MAPK Signaling Up-regulates the Activity of Hypoxia-inducible Factors by Its Effects on p300

Sang, Nianli; Stiehl, Daniel P.; Bohensky, Jolene; Leshchinsky, Irene; Srinivas, Vickram; Caro, Jaime

doi:10.1074/jbc.m209702200

Cited by 370Cancer, Hypoxia, and MetabolismKruppel-like factors researchAngiogenesis and VEGF in Cancer

MAPK Signaling Up-regulates the Activity of Hypoxia-inducible Factors by Its Effects on p300

Open access

Sang, Nianli, Stiehl, Daniel P., Bohensky, Jolene, Leshchinsky, Irene, Srinivas, Vickram, Caro, Jaime·2003·Journal of Biological Chemistry

DOI 10.1074/jbc.m209702200PMC PMC4518846

Open this paper in CoChat — free account Open PDF

Abstract

Hypoxia-inducible factors (HIF) are a family of heterodimeric transcriptional regulators that play pivotal roles in the regulation of cellular utilization of oxygen and glucose and are essential transcriptional regulators of angiogenesis in solid tumor and ischemic disorders. The transactivation activity of HIF complexes requires the recruitment of p300/CREB-binding protein (CBP) by HIF-1 alpha and HIF-2 alpha that undergo oxygen-dependent degradation. HIF activation in tumors is caused by several factors including mitogen-activated protein kinase (MAPK) signaling. Here we investigated the molecular basis for HIF activation by MAPK. We show that MAPK is required for the transactivation activity of HIF-1 alpha. Furthermore, inhibition of MAPK disrupts the HIF-p300 interaction and suppresses the transactivation activity of p300. Overexpression of MEK1, an upstream MAPK activator, stimulates the transactivation of both p300 and HIF-1 alpha. Interestingly, the C-terminal transactivation domain of HIF-1 alpha is not a direct substrate of MAPK, and HIF-1 alpha phosphorylation is not required for HIF-CAD/p300 interaction. Taken together, our data suggest that MAPK signaling facilitates HIF activation through p300/CBP.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1074/jbc.m209702200

Cites

55 of 55 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Activated ERK phosphorylates 4E-BP1, S6K, and MNK.
“Activated ERK phosphorylates 4E-BP1, S6K, and MAP kinase interacting kinase (MNK).”
From HIF-1α pathway: role, regulation and intervention for cancer therapy (2015) · cites this paper as [39]
The paper describes ERK1/2 as kinases that phosphorylate nuclear substrates and reports MAPK phosphorylation of p300 in the Discussion (page not provided). Searches for 4E-BP1, S6K, and MNK found no passage identifying them as ERK substrates in our copy. (LLM, conf=0.75)
Experimental — accuracy not yet measured
MNK can phosphorylate eIF-4E directly.
“MNK can also phosphorylate eIF-4E directly39.”
From HIF-1α pathway: role, regulation and intervention for cancer therapy (2015) · cites this paper as [39]
The results section and Discussion describe MAPK phosphorylation of HIF-1α and p300, not MNK phosphorylation of eIF-4E. Searches of our full-text copy for MNK and eIF-4E found no passage addressing the claimed reaction. (LLM, conf=0.76)
Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Angiogenesis in cancer, vascular, rheumatoid and other disease
Folkman, J. (1995) · Nature Medicine · doi:10.1038/nm0195-27 · Cited by 7,627 · see citing works
Targeting of HIF-α to the von Hippel-Lindau Ubiquitylation Complex by O 2 -Regulated Prolyl Hydroxylation
Jaakkola, P., Mole, D. R., Tian, Y.-M., Wilson, M. I., Gielbert, J., Gaskell, S. J., Kriegsheim, A. V., Hebestreit, H. F., Mukherji, M., Schofield, C. J., et al. (2001) · Science · doi:10.1126/science.1059796 · Cited by 5,535 · see citing works
HIFα Targeted for VHL-Mediated Destruction by Proline Hydroxylation: Implications for O 2 Sensing
Ivan, M., Kondo, K., Yang, H., Kim, W., Valiando, J., Ohh, M., Salic, A., Asara, J. M., Lane, W. S., & Kaelin Jr., W. G. (2001) · Science · doi:10.1126/science.1059817 · Cited by 4,735 · see citing works
PD 098059 Is a Specific Inhibitor of the Activation of Mitogen-activated Protein Kinase Kinase in Vitro and in Vivo
Alessi, D. R., Cuenda, A., Cohen, P., Dudley, D. T., & Saltiel, A. R. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.46.27489 · Cited by 3,396 · see citing works
C. elegans EGL-9 and mammalian homologs define a family of dioxygenases that regulate HIF by prolyl hydroxylation
Epstein, A. C. R., Gleadle, J. M., McNeill, L. A., Hewitson, K. S., O'Rourke, J., Mole, D. R., Mukherji, M., Metzen, E., Wilson, M. I., Dhanda, A., et al. (2001) · Cell · doi:10.1016/s0092-8674(01)00507-4 · Cited by 3,333 · see citing works
A conserved family of prolyl-4-hydroxylases that modify HIF
Bruick, R. K., & McKnight, S. L. (2001) · Science · doi:10.1126/science.1066373 · Cited by 2,549 · see citing works
Regulation of hypoxia-inducible factor 1α is mediated by an O 2 -dependent degradation domain via the ubiquitin-proteasome pathway
Huang, L. E., Gu, J., Schau, M., & Bunn, H. F. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.14.7987 · Cited by 2,113 · see citing works
Regulation of Mammalian O 2 Homeostasis by Hypoxia-Inducible Factor 1
Semenza, G. L. (1999) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.15.1.551 · Cited by 1,914 · see citing works
Hypoxia-inducible Factor 1α (HIF-1α) Protein Is Rapidly Degraded by the Ubiquitin-Proteasome System under Normoxic Conditions
Salceda, S., & Caro, J. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.36.22642 · Cited by 1,674 · see citing works
Self-citation
Asparagine Hydroxylation of the HIF Transactivation Domain: A Hypoxic Switch
Lando, D., Peet, D. J., Whelan, D. A., Gorman, J. J., & Whitelaw, M. L. (2002) · Science · doi:10.1126/science.1068592 · Cited by 1,558 · see citing works
FIH-1 is an asparaginyl hydroxylase enzyme that regulates the transcriptional activity of hypoxia-inducible factor
Lando, D., Peet, D. J., Gorman, J. J., Whelan, D. A., Whitelaw, M. L., & Bruick, R. K. (2002) · Genes & Development · doi:10.1101/gad.991402 · Cited by 1,550 · see citing works
Untitled work
(2000) · PubMed · Cited by 1,445 · see citing works
FIH-1: a novel protein that interacts with HIF-1α and VHL to mediate repression of HIF-1 transcriptional activity
Mahon, P. C., Hirota, K., & Semenza, G. L. (2001) · Genes & Development · doi:10.1101/gad.924501 · Cited by 1,385 · see citing works
Transformation of Mammalian Cells by Constitutively Active MAP Kinase Kinase
Mansour, S. J., Matten, W. T., Hermann, A. S., Candia, J. M., Rong, S., Fukasawa, K., Woude, G. F. V., & Ahn, N. G. (1994) · Science · doi:10.1126/science.8052857 · Cited by 1,355 · see citing works
HER2 (neu) Signaling Increases the Rate of Hypoxia-Inducible Factor 1α (HIF-1α) Synthesis: Novel Mechanism for HIF-1-Mediated Vascular Endothelial Growth Factor Expression
Laughner, E., Taghavi, P., Chiles, K., Mahon, P. C., & Semenza, G. L. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.12.3995-4004.2001 · Cited by 1,256 · see citing works
Activation of Hypoxia-inducible Transcription Factor Depends Primarily upon Redox-sensitive Stabilization of Its α Subunit
Huang, E. L., Arany, Z. P., Livingston, D. M., & Bunn, H. F. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.50.32253 · Cited by 1,190 · see citing works
Independent function of two destruction domains in hypoxia-inducible factor-α chains activated by prolyl hydroxylation
Masson, N., Willam, C., Maxwell, P. H., Pugh, C. W., & Ratcliffe, P. J. (2001) · The EMBO Journal · doi:10.1093/emboj/20.18.5197 · Cited by 1,014 · see citing works
CREB-binding Protein and p300 in Transcriptional Regulation
Vo, N., & Goodman, R. H. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.r000025200 · Cited by 868 · see citing works
Loss of PTEN facilitates HIF-1-mediated gene expression
Zundel, W., Schindler, C., Haas-Kogan, D., Koong, A., Kaper, F., Chen, E., Gottschalk, A. R., Ryan, H. E., Johnson, R. S., Jefferson, A. B., et al. (2000) · Genes & Development · doi:10.1101/gad.14.4.391 · Cited by 840 · see citing works
HIF-1α binding to VHL is regulated by stimulus-sensitive proline hydroxylation
Yu, F., White, S. B., Zhao, Q., & Lee, F. S. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.181341498 · Cited by 796 · see citing works
p42/p44 Mitogen-activated Protein Kinases Phosphorylate Hypoxia-inducible Factor 1α (HIF-1α) and Enhance the Transcriptional Activity of HIF-1
Richard, D. E., Berra, E., Gothié, E., Roux, D., & Pouysségur, J. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.46.32631 · Cited by 790 · see citing works
An essential role for p300/CBP in the cellular response to hypoxia
Arany, Z., Huang, L. E., Eckner, R., Bhattacharya, S., Jiang, C., Goldberg, M. A., Bunn, H. F., & Livingston, D. M. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.23.12969 · Cited by 790 · see citing works
Rbx1, a Component of the VHL Tumor Suppressor Complex and SCF Ubiquitin Ligase
Kamura, T., Koepp, D. M., Conrad, M. N., Skowyra, D., Moreland, R. J., Iliopoulos, O., Lane, W. S., Kaelin, W. G., Elledge, S. J., Conaway, R. C., et al. (1999) · Science · doi:10.1126/science.284.5414.657 · Cited by 786 · see citing works
Structure of an HIF-1α-pVHL Complex: Hydroxyproline Recognition in Signaling
Min, J.-H., Yang, H., Ivan, M., Gertler, F., Kaelin, W. G., & Pavletich, N. P. (2002) · Science · doi:10.1126/science.1073440 · Cited by 765 · see citing works
Hypoxia-inducible factor (HIF) asparagine hydroxylase is identical to factor inhibiting HIF (FIH) and is related to the cupin structural family
Hewitson, K. S., McNeill, L. A., Riordan, M. V., Tian, Y.-M., Bullock, A. N., Welford, R. W., Elkins, J. M., Oldham, N. J., Bhattacharya, S., Gleadle, J. M., et al. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.c200273200 · Cited by 719 · see citing works
Activation of HIF1α ubiquitination by a reconstituted von Hippel-Lindau (VHL) tumor suppressor complex
Kamura, T., Sato, S., Iwaï, K., Czyzyk-Krzeska, M., Conaway, R. C., & Conaway, J. W. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.190332597 · Cited by 652 · see citing works
Transactivation and Inhibitory Domains of Hypoxia-inducible Factor 1α
Jiang, B.-H., Zheng, J. Z., Leung, S. W., Roe, R., & Semenza, G. L. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.31.19253 · Cited by 629 · see citing works
Activation of Hypoxia-inducible Factor-1; Definition of Regulatory Domains within the α Subunit
Pugh, C. W., O'Rourke, J. F., Nagao, M., Gleadle, J., & Ratcliffe, P. J. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.17.11205 · Cited by 526 · see citing works
Structural basis for recruitment of CBP/p300 by hypoxia-inducible factor-1α
Freedman, S. J., Sun, Z., Poy, F., Kung, A. L., Livingston, D. M., Wagner, G., & Eck, M. J. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.082117899 · Cited by 457 · see citing works
Activation of the HIF pathway in cancer
Maxwell, P. H. (2001) · Current Opinion in Genetics & Development · doi:10.1016/s0959-437x(00)00193-3 · Cited by 426 · see citing works
Structural basis for Hif-1α/CBP recognition in the cellular hypoxic response
Dames, S. A., Martinez‐Yamout, M. A., Guzman, R. N. D., Dyson, H. J., & Wright, P. E. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.082121399 · Cited by 404 · see citing works
ERK activation upon hypoxia: involvement in HIF‐1 activation
Minet, E., Arnould, T., Michel, G., Roland, I., Mottet, D., Raes, M. J., Remacle, J., & Michiels, C. (2000) · FEBS Letters · doi:10.1016/s0014-5793(00)01181-9 · Cited by 380 · see citing works
Cloning and characterization of two distinct human extracellular signal-regulated kinase activator kinases, MEK1 and MEK2
Zheng, C. F., & Guan, K. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)82142-1 · Cited by 336 · see citing works
Normoxic induction of the hypoxia‐inducible factor 1α by insulin and interleukin‐1β involves the phosphatidylinositol 3‐kinase pathway
Stiehl, D. P., JELKMANN, W. E. B., Wenger, R. H., & Hellwig‐Bürgel, T. (2002) · FEBS Letters · doi:10.1016/s0014-5793(02)02247-0 · Cited by 285 · see citing works
Self-citation
Effect of Protein Kinase and Phosphatase Inhibitors on Expression of Hypoxia Inducible Factor 1
Wang, G. L., Jiang, B., & Semenza, G. L. (1995) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1995.2674 · Cited by 230 · see citing works
MAP Kinase-Dependent Transcriptional Coactivation by Elk-1 and Its Cofactor CBP
Janknecht, R., & Nordheim, A. (1996) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1996.1740 · Cited by 191 · see citing works
The mitogen activated protein kinase signal transduction pathway: From the cell surface to the nucleus
Guan, K. (1994) · Cellular Signalling · doi:10.1016/0898-6568(94)90041-8 · Cited by 186 · see citing works
EPAS1 trans-activation during hypoxia requires p42/p44 MAPK
Conrad, P. W., Freeman, T. L., Beitner-Johnson, D., & Millhorn, D. E. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.47.33709 · Cited by 178 · see citing works
Phosphatidylinositol 3-Kinase/Akt Signaling Is Neither Required for Hypoxic Stabilization of HIF-1α nor Sufficient for HIF-1-dependent Target Gene Transcription
Arsham, A. M., Plas, D. R., Thompson, C. B., & Simon, M. C. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m111162200 · Cited by 175 · see citing works
MAPK and Akt Act Cooperatively but Independently on Hypoxia Inducible Factor-1α in rasV12 Upregulation of VEGF
Sodhi, A., Montaner, S., Miyazaki, H., & Gutkind, J. S. (2001) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2001.5532 · Cited by 161 · see citing works
Carboxyl-Terminal Transactivation Activity of Hypoxia-Inducible Factor 1α Is Governed by a von Hippel-Lindau Protein-Independent, Hydroxylation-Regulated Association with p300/CBP
Sang, N., Fang, J., Srinivas, V., Leshchinsky, I., & Caro, J. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.9.2984-2992.2002 · Cited by 143 · see citing works
Self-citation
Characterization of an Oxygen/Redox-Dependent Degradation Domain of Hypoxia-Inducible Factor α (HIF-α) Proteins
Srinivas, V., Zhang, L.-P., Zhu, X.-H., & Caro, J. (1999) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1999.0878 · Cited by 140 · see citing works
Self-citation
Molecular Mechanism of Hypoxia-inducible Factor 1α-p300 Interaction
Gu, J., Milligan, J., & Huang, E. L. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m009522200 · Cited by 130 · see citing works
CBP/p300 Integrates Raf/Rac-Signaling Pathways in the Transcriptional Induction of NF-ATc during T Cell Activation
Avots, A., Buttmann, M., Chuvpilo, S. A., Escher, C., Smola, U., Bannister, A. J., Rapp, U. R., Kouzarides, T., & Serfling, E. (1999) · Immunity · doi:10.1016/s1074-7613(00)80051-5 · Cited by 125 · see citing works
Cell-type specific regulation of human interstitial collagenase-1 gene expression by interleukin-1β (IL-1β) in human fibroblasts and BC-8701 breast cancer cells
Rutter, J. L., Benbow, U., Coon, C. I., & Brinckerhoff, C. (1997) · Journal of Cellular Biochemistry · doi:10.1002/(sici)1097-4644(19970901)66:3 · Cited by 121 · see citing works
Mechanical stimulation of osteopontin mRNA expression and synthesis in bone cell cultures
Klein‐Nulend, J., Roelofsen, J., Semeins, C. M., Bronckers, A. L. J. J., & Burger, E. H. (1997) · Journal of Cellular Physiology · doi:10.1002/(sici)1097-4652(199702)170:2 · Cited by 115 · see citing works
Self-citation
The Transcriptional Activation Function of the HIF-like Factor Requires Phosphorylation at a Conserved Threonine
Gradin, K., Takasaki, C., Fujii‐Kuriyama, Y., & Sogawa, K. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m201307200 · Cited by 105 · see citing works
The Transcriptional Co-activators CBP and p300 Are Activated via Phenylephrine through the p42/p44 MAPK Cascade
Gusterson, R. J., Brar, B. K., Faulkes, D. J., Giordano, A., Chrivia, J. C., & Latchman, D. S. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m104626200 · Cited by 98 · see citing works
Regulation of Gene Expression by the Hypoxia-Inducible Factors
Fedele, A. O. (2002) · Molecular Interventions · doi:10.1124/mi.2.4.229 · Cited by 86 · see citing works
Hypoxia Regulation of Gene Transcription
Caro, J. (2001) · High Altitude Medicine & Biology · doi:10.1089/152702901750265251 · Cited by 80 · see citing works
Activation of Mitogen-activated Protein Kinase Cascade Regulates Pituitary Tumor-transforming Gene Transactivation Function
Pei, L. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m002451200 · Cited by 78 · see citing works
Complex role of protein phosphorylation in gene activation by hypoxia
Salceda, S., Beck, I., Srinivas, V., & Caro, J. (1997) · Kidney International · doi:10.1038/ki.1997.78 · Cited by 73 · see citing works
Self-citation
Stimulation of p300-mediated Transcription by the Kinase MEKK1
See, R. H., Calvo, D., Shi, Y. G., Kawa, H., Luke, M. P.-S., Yuan, Z., & Shi, Y. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m008113200 · Cited by 55 · see citing works
Adenoviral E1A everlasting tool versatile applications continuous contributions and new hypotheses
Sang, N. (2002) · Frontiers in bioscience · doi:10.2741/a784 · Cited by 31 · see citing works
Self-citation
Mast cell tryptase does not alter matrix metalloproteinase expression in human dermal fibroblasts: Further evidence that proteolytically-active tryptase is a potent fibrogenic factor
Zhang, J., Gruber, B. L., Marchese, M. J., Zucker, S., Schwartz, L. B., & Kew, R. R. (1999) · Journal of Cellular Physiology · doi:10.1002/(sici)1097-4652(199911)181:2 · Cited by 16 · see citing works

Flagged first, then by citations

Research works printed but not linked: 6

Huang, L. E., Gu, J., Schau, M., and Bunn, H. F. (1998) Proc. Natl. Acad. Sci.
Yu, F., White, S. B., Zhao, Q., and Lee, F. S. (2001) Proc. Natl. Acad. Sci.
Kamura, T., Sato, S., Iwai, K., Czyzyk-Krzeska, M., Conaway, R. C., and Conaway, J. W. (2000) Proc. Natl. Acad. Sci. U. S. A. 97, 10430 -10435
Arany, Z., Huang, L. E., Eckner, R., Bhattacharya, S. Jiang, C., Goldberg, M. A., Bunn, H. F., and Livingston, D. M. (1996) Proc. Natl. Acad. Sci.
Dames, S. A., Martinez-Yamout, M., DeGuzman, R. N., Dyson, H. J., and Wright, P. E. (2002) Proc. Natl. Acad. Sci. U. S. A. 99, 5271-5276
Freedman, S. J., Sun, Z. Y. J., Poy, F., Kung, A. L., Livingston, D. M., Wagner, G., and Eck, M. J. (2002) Proc. Natl. Acad. Sci. U. S. A. 99, 5367-5372

Sorted by citations

Targeting HIF-1 for cancer therapy
Semenza, G. L. (2003) · Nature Reviews Cancer · doi:10.1038/nrc1187 · Cited by 6,717 · see citing works
HIF-1α pathway: role, regulation and intervention for cancer therapy
Masoud, G. N., & Li, W. (2015) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2015.05.007 · Cited by 1,871 · see citing works
A Comprehensive Review on MAPK: A Promising Therapeutic Target in Cancer
Braicu, C., Buse, M., Busuioc, C. I., Drulă, R., Gulei, D., Ráduly, L., Alexandru Vasile, R. U. S. U., Irimie, A., Atanasov, A. G., Slaby, O., et al. (2019) · Cancers · doi:10.3390/cancers11101618 · Cited by 940 · see citing works
Tumour hypoxia induces a metabolic shift causing acidosis: a common feature in cancer
Chiche, J., Brahimi-Horn, M. C., & Pouysségur, J. (2010) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2009.00994.x · Cited by 671 · see citing works
5-Hydroxymethylfurfural (HMF) levels in honey and other food products: effects on bees and human health
Shapla, U. M., Solayman, M., Alam, N., Khalil, M. I., & Gan, S. H. (2018) · Chemistry Central Journal · doi:10.1186/s13065-018-0408-3 · Cited by 586 · see citing works
Mitogen-Activated Protein (MAP) Kinase/MAP Kinase Phosphatase Regulation: Roles in Cell Growth, Death, and Cancer
Boutros, T., Chevet, É., & Metrakos, P. P. (2008) · Pharmacological Reviews · doi:10.1124/pr.107.00106 · Cited by 545 · see citing works
Hypoxia-inducible factor 1: regulation by hypoxic and non-hypoxic activators
Déry, M.-A. C., Michaud, M. D., & Richard, D. E. (2004) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2004.08.012 · Cited by 545 · see citing works
Hypoxia signaling in human health and diseases: implications and prospects for therapeutics
Luo, Z., Tian, M., Yang, G., Tan, Q., Chen, Y., Li, G., Zhang, Q., Li, Y., Wan, P., & Wu, J. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01080-1 · Cited by 499 · see citing works
The MAPK and AMPK signalings: interplay and implication in targeted cancer therapy
Yuan, J., Dong, X., Yap, J., & Hu, J. (2020) · Journal of Hematology & Oncology · doi:10.1186/s13045-020-00949-4 · Cited by 500 · see citing works
Transcriptional regulation by the MAP kinase signaling cascades
Yang, S., Sharrocks, A. D., & Whitmarsh, A. J. (2003) · Gene · doi:10.1016/s0378-1119(03)00816-3 · Cited by 489 · see citing works
Pathophysiological mechanisms and therapeutic approaches in obstructive sleep apnea syndrome
Lv, R., Liu, X., Zhang, Y., Dong, N., Wang, X., He, Y., Yue, H., & Yin, Q. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01496-3 · Cited by 521 · see citing works
Regulation of Hypoxia-Inducible Factor-1a by Reactive Oxygen Species : New Developments in an Old Debate
Movafagh, S., Crook, S., & Vo, K. (2015) · Journal of Cellular Biochemistry · doi:10.1002/jcb.25074 · Cited by 469 · see citing works
Bacterial lipopolysaccharide induces HIF-1 activation in human monocytes via p44/42 MAPK and NF-κB
Frede, S., Stockmann, C., Freitag, P., & Fandrey, J. (2006) · Biochemical Journal · doi:10.1042/bj20051839 · Cited by 436 · see citing works
The transcriptional factors HIF-1 and HIF-2 and their novel inhibitors in cancer therapy
Albadari, N. G., Deng, S., & Li, W. (2019) · Expert Opinion on Drug Discovery · doi:10.1080/17460441.2019.1613370 · Cited by 351 · see citing works
Hypoxia inducible factor-1α as a cancer drug target
Powis, G., & Kirkpatrick, L. (2004) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.647.3.5 · Cited by 311 · see citing works
Signaling Pathways for Early Brain Injury after Subarachnoid Hemorrhage
Kusaka, G., Ishikawa, M., Nanda, A., Granger, D. N., & Zhang, J. H. (2004) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1097/01.wcb.0000125886.48838.7e · Cited by 319 · see citing works
Glycolysis in cancer: A potential target for therapy
Gatenby, R. A., & Gillies, R. J. (2007) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2007.03.021 · Cited by 305 · see citing works
Direct transcriptional up-regulation of cyclooxygenase-2 by hypoxia-inducible factor (HIF)-1 promotes colorectal tumor cell survival and enhances HIF-1 transcriptional activity during hypoxia
Kaidi, A., Qualtrough, D., Williams, A. C., & Paraskeva, C. (2006) · Cancer Research · doi:10.1158/0008-5472.can-06-0425 · Cited by 300 · see citing works
Hypoxia signaling pathways in cancer metabolism: the importance of co-selecting interconnected physiological pathways
Masson, N., & Ratcliffe, P. J. (2014) · Cancer & Metabolism · doi:10.1186/2049-3002-2-3 · Cited by 296 · see citing works
Negative and positive regulation of HIF-1: A complex network
Bárdos, J. I., & Ashcroft, M. A. (2005) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2005.05.001 · Cited by 282 · see citing works
Recent advances in hypoxia-inducible factor (HIF)-1 inhibitors
Xia, Y., Choi, H.-K., & Lee, K. (2012) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2012.01.033 · Cited by 278 · see citing works
Identification of MAPK Phosphorylation Sites and Their Role in the Localization and Activity of Hypoxia-inducible Factor-1α
Mylonis, I., Chachami, G., Samiotaki, M. K., Panayotou, G., Paraskeva, E., Kalousi, A., Georgatsou, E., Bonanou, S., & Simos, G. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m605058200 · Cited by 266 · see citing works
Genistein Inhibits Prostate Cancer Cell Growth by Targeting miR-34a and Oncogenic HOTAIR
Chiyomaru, T., Yamamura, S., Fukuhara, S., Yoshino, H., Kinoshita, T., Majid, S., Saini, S., Chang, I., Tanaka, Y., Enokida, H., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0070372 · Cited by 265 · see citing works
Hypoxia, hypoxia-inducible factors (HIF), HIF hydroxylases and oxygen sensing
Webb, J. D., Coleman, M. L., & Pugh, C. W. (2009) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-009-0147-7 · Cited by 255 · see citing works
Review: Hypoxia-Inducible Factor-1 (HIF-1): A Novel Transcription Factor in Immune Reactions
Hellwig‐Bürgel, T., Stiehl, D. P., Wagner, A. E., Metzen, E., & JELKMANN, W. E. B. (2005) · Journal of Interferon & Cytokine Research · doi:10.1089/jir.2005.25.297 · Cited by 255 · see citing works
Self-citation
Transcriptional control of the tumor- and hypoxia-marker carbonic anhydrase 9: A one transcription factor (HIF-1) show?
Kaluz, Š., Kaluzová, M., Liao, S., Lerman, M. I., & Stanbridge, E. J. (2009) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2009.01.001 · Cited by 251 · see citing works
Ca2+/Calmodulin Kinase-dependent Activation of Hypoxia Inducible Factor 1 Transcriptional Activity in Cells Subjected to Intermittent Hypoxia
Yuan, G., Nanduri, J., Bhasker, C. R., Semenza, G. L., & Prabhakar, N. R. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m407706200 · Cited by 242 · see citing works
Molecular mechanisms of early brain injury after subarachnoid hemorrhage
Ostrowski, R. P., Colohan, A. R. T., & Zhang, J. H. (2006) · Neurological Research · doi:10.1179/016164106x115008 · Cited by 241 · see citing works
Turn me on: regulating HIF transcriptional activity
Lisy, K., & Peet, D. J. (2008) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4402315 · Cited by 235 · see citing works
Nitric Oxide Induces Hypoxia-inducible Factor 1 Activation That Is Dependent on MAPK and Phosphatidylinositol 3-Kinase Signaling
Kasuno, K., Takabuchi, S., Fukuda, K., Kizaka‐Kondoh, S., Yodoi, J., Adachi, T., Semenza, G. L., & Hirota, K. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m308197200 · Cited by 223 · see citing works
Retracted
Chemoresistance and the Self-Maintaining Tumor Microenvironment
Yeldag, G., Rice, A. J., & Hernández, A. E. D. R. (2018) · Cancers · doi:10.3390/cancers10120471 · Cited by 211 · see citing works
Signalling via the hypoxia-inducible factor-1α requires multiple posttranslational modifications
Brahimi‐Horn, C., Mazure, N. M., & Pouysségur, J. (2004) · Cellular Signalling · doi:10.1016/j.cellsig.2004.04.010 · Cited by 213 · see citing works
Reactive oxygen species and HIF-1 signalling in cancer
Galanis, Α., Pappa, A., Giannakakis, A., Lanitis, E., Laniti, D. D., & Sandaltzopoulos, R. (2008) · Cancer Letters · doi:10.1016/j.canlet.2008.02.028 · Cited by 207 · see citing works
Hypoxia inducible factors in liver disease and hepatocellular carcinoma: Current understanding and future directions
Wilson, G. K., Tennant, D. A., & McKeating, J. A. (2014) · Journal of Hepatology · doi:10.1016/j.jhep.2014.08.025 · Cited by 201 · see citing works
Hypoxia‐inducible factor‐1 and oncogenic signalling
Bárdos, J. I., & Ashcroft, M. A. (2004) · BioEssays · doi:10.1002/bies.20002 · Cited by 204 · see citing works
Regulation of Nrf2 Transactivation Domain Activity
Shen, G., Hebbar, V., Nair, S., Xu, C., Li, W., Lin, W., Keum, Y.-S., Han, J., Gallo, M. A., & Kong, A.-N. T. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m401368200 · Cited by 194 · see citing works
The mRNA related ceRNA–ceRNA landscape and significance across 20 major cancer types
Xu, J., Li, Y., Lu, J., Pan, T., Ding, N., Wang, Z., Shao, T., Zhang, J., Wang, L., & Li, X. (2015) · Nucleic Acids Research · doi:10.1093/nar/gkv853 · Cited by 192 · see citing works
Molecular Mechanisms for Early Brain Injury After Subarachnoid Hemorrhage
Ostrowski, R. P., Colohan, A. R. T., & Zhang, J. H. (2006) · Springer eBooks · doi:10.1007/978-0-387-30383-3_13 · Cited by 192 · see citing works
HIFs and tumors—causes and consequences
Höpfl, G., Ogunshola, O. O., & Gassmann, M. (2004) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00538.2003 · Cited by 185 · see citing works
Genistein Up-Regulates Tumor Suppressor MicroRNA-574-3p in Prostate Cancer
Chiyomaru, T., Yamamura, S., Fukuhara, S., Hidaka, H., Majid, S., Saini, S., Arora, S., Deng, G., Shahryari, V., Chang, I., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0058929 · Cited by 175 · see citing works
Hypoxia-Inducible Factors (HIFs) and Phosphorylation: Impact on Stability, Localization, and Transactivity
Kietzmann, T., Mennerich, D., & Dimova, E. Y. (2016) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2016.00011 · Cited by 176 · see citing works
HIF hydroxylation and cellular oxygen sensing
Metzen, E., & Ratcliffe, P. J. (2004) · Biological Chemistry · doi:10.1515/bc.2004.016 · Cited by 171 · see citing works
Central Role of Muc5ac Expression in Mucous Metaplasia and Its Regulation by Conserved 5′ Elements
Young, H. W. J., Williams, O. W., Chandra, D., Bellinghausen, L. K., Pérez, G., Suárez, A. V., Tuvim, M. J., Roy, M. G., Alexander, S., Moghaddam, S. J., et al. (2007) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2005-0460oc · Cited by 169 · see citing works
Targeting Multiple Signaling Pathways as a Strategy for Managing Prostate Cancer: Multifocal Signal Modulation Therapy
McCarty, M. F. (2004) · Integrative Cancer Therapies · doi:10.1177/1534735404270757 · Cited by 170 · see citing works
Regulation of gene expression by hypoxia: Integration of the HIF-transduced hypoxic signal at the hypoxia-responsive element
Kaluz, Š., Kaluzová, M., & Stanbridge, E. J. (2008) · Clinica Chimica Acta · doi:10.1016/j.cca.2008.05.002 · Cited by 171 · see citing works
Overexpression of hypoxia-inducible factor and metabolic pathways: possible targets of cancer
Singh, D. P., Arora, R., Kaur, P., Singh, B., Mannan, R., & Arora, S. (2017) · Cell & Bioscience · doi:10.1186/s13578-017-0190-2 · Cited by 166 · see citing works
Metabolic reprogramming of proinflammatory macrophages by target delivered roburic acid effectively ameliorates rheumatoid arthritis symptoms
Jia, N., Gao, Y., Li, M., Liang, Y., Li, Y., Lin, Y., Huang, S., Lin, Q., Sun, X., He, Q., et al. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01499-0 · Cited by 160 · see citing works
Regulation of hypoxia-inducible factor 1 and the loss of the cellular response to hypoxia in diabetes
Bento, C. F., & Pereira, P. (2011) · Diabetologia · doi:10.1007/s00125-011-2191-8 · Cited by 159 · see citing works
Hypoxia inducible factor (HIF) in rheumatology: low O2! See what HIF can do!
Gaber, T., Dziurla, R., Tripmacher, R., Burmester, G. R., & Buttgereit, F. (2005) · Annals of the Rheumatic Diseases · doi:10.1136/ard.2004.031641 · Cited by 156 · see citing works
HIF-1: master and commander of the hypoxic world
Mazure, N. M., Brahimi-Horn, M. C., Berta, M., Benizri, E. I., Bilton, R. L., Dayan, F., Ginouvès, A., Berra, E., & Pouysségur, J. (2004) · Biochemical Pharmacology · doi:10.1016/j.bcp.2004.04.022 · Cited by 152 · see citing works
A Comprehensive and System Review for the Pharmacological Mechanism of Action of Rhein, an Active Anthraquinone Ingredient
Sun, H., Luo, G., Chen, D., & Xiang, Z. (2016) · Frontiers in Pharmacology · doi:10.3389/fphar.2016.00247 · Cited by 142 · see citing works
The expression of hypoxia-inducible factor 1alpha is a favorable independent prognostic factor in renal cell carcinoma.
Lidgren, A., Hedberg, Y., Grankvist, K., Rasmuson, T., Vasko, J., & Ljungberg, B. (2005) · PubMed · Cited by 139 · see citing works
p300 relieves p53-evoked transcriptional repression of hypoxia-inducible factor-1 (HIF-1)
Schmid, T., Zhou, J., Köhl, R., & Brüne, B. (2004) · Biochemical Journal · doi:10.1042/bj20031299 · Cited by 138 · see citing works
The role of hypoxia-inducible factors in cancer
Maynard, M. A., & Ohh, M. (2007) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-007-7082-2 · Cited by 138 · see citing works
Kinase requirements in human cells: III. Altered kinase requirements in VHL −/− cancer cells detected in a pilot synthetic lethal screen
Bommi‐Reddy, A., Almeciga, I., Sawyer, J., Geisen, C., Li, W., Harlow, E., Kaelin, W. G., & Grueneberg, D. A. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0806574105 · Cited by 138 · see citing works
Regulation of Hypoxia‐Inducible Factors During Inflammation
Frede, S., Berchner‐Pfannschmidt, U., & Fandrey, J. (2007) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(07)35021-0 · Cited by 136 · see citing works
Bortezomib represses HIF-1α protein expression and nuclear accumulation by inhibiting both PI3K/Akt/TOR and MAPK pathways in prostate cancer cells
Befani, C. D., Vlachostergios, P. J., Hatzidaki, E., Patrikidou, A., Bonanou, S., Simos, G., Papandreou, C. N., & Liakos, P. (2012) · Journal of Molecular Medicine · doi:10.1007/s00109-011-0805-8 · Cited by 135 · see citing works
Recent developments in the regulation of the angiogenic switch by cellular stress factors in tumors
North, S., Moenner, M., & Bikfalvi, A. (2004) · Cancer Letters · doi:10.1016/j.canlet.2004.08.007 · Cited by 136 · see citing works
Estrogen-Induced Activation of Hypoxia-Inducible Factor-1α, Vascular Endothelial Growth Factor Expression, and Edema in the Uterus Are Mediated by the Phosphatidylinositol 3-Kinase/Akt Pathway
Kazi, A. A., & Koos, R. D. (2007) · Endocrinology · doi:10.1210/en.2006-1394 · Cited by 132 · see citing works
Transcriptional responses to intermittent hypoxia
Nanduri, J., Yuan, G., Kumar, G. K., Semenza, G. L., & Prabhakar, N. R. (2008) · Respiratory Physiology & Neurobiology · doi:10.1016/j.resp.2008.07.006 · Cited by 130 · see citing works
Systematic and comprehensive insights into HIF-1 stabilization under normoxic conditions: implications for cellular adaptation and therapeutic strategies in cancer
Zhang, J., Yao, M., Xia, S., Zeng, F., & Liu, Q. (2025) · Cellular & Molecular Biology Letters · doi:10.1186/s11658-024-00682-7 · Cited by 139 · see citing works
The potential role of HIF on tumour progression and dissemination
Unwith, S., Zhao, H., Hennah, L., & Ma, D. (2014) · International Journal of Cancer · doi:10.1002/ijc.28889 · Cited by 126 · see citing works
Metal-induced carcinogenesis, oxidative stress and hypoxia signalling
Galanis, Α., Karapetsas, A., & Sandaltzopoulos, R. (2008) · Mutation Research/Genetic Toxicology and Environmental Mutagenesis · doi:10.1016/j.mrgentox.2008.10.008 · Cited by 125 · see citing works
The role of Hypoxia-Inducible Factor-1alpha and its signaling in melanoma
Malekan, M., Ebrahimzadeh, M. A., & Sheida, F. (2021) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2021.111873 · Cited by 123 · see citing works
Identification of a Novel Small Molecule HIF-1α Translation Inhibitor
Narita, T., Yin, S., Gelin, C. F., Moreno, C. S., Yepes, M., Nicolaou, K. C., & Meir, E. G. V. (2009) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-08-3180 · Cited by 123 · see citing works
The antiepidermal growth factor receptor monoclonal antibody cetuximab/C225 reduces hypoxia-inducible factor-1 alpha, leading to transcriptional inhibition of vascular endothelial growth factor expression
Luwor, R. B., Lü, Y., Li, X., Mendelsohn, J. M., & Fan, Z. (2005) · Oncogene · doi:10.1038/sj.onc.1208625 · Cited by 122 · see citing works
Role of the Phosphatidylinositol-3-Kinase and Extracellular Regulated Kinase Pathways in the Induction of Hypoxia-Inducible Factor (HIF)-1 Activity and the HIF-1 Target Vascular Endothelial Growth Factor in Ovarian Granulosa Cells in Response to Follicle-Stimulating Hormone
Alam, H., Weck, J., Maizels, E. T., Park, Y., Lee, E. J., Ashcroft, M. A., & Hunzicker-Dunn, M. E. (2008) · Endocrinology · doi:10.1210/en.2008-0850 · Cited by 121 · see citing works
HIF at the crossroads between ischemia and carcinogenesis
Paul, S., Simons, J. W., & Mabjeesh, N. J. (2004) · Journal of Cellular Physiology · doi:10.1002/jcp.10479 · Cited by 121 · see citing works
Treatment of kidney cancer
Kaelin, W. G. (2009) · Cancer · doi:10.1002/cncr.24232 · Cited by 119 · see citing works
Hypoxia, drug therapy and toxicity
Lee, K., Roth, R. A., & LaPres, J. J. (2006) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2006.08.001 · Cited by 118 · see citing works
The Expression of Hypoxia-Inducible Factor 1α Is a Favorable Independent Prognostic Factor in Renal Cell Carcinoma
Lidgren, A., Hedberg, Y., Grankvist, K., Rasmuson, T., Vasko, J., & Ljungberg, B. (2005) · Clinical Cancer Research · doi:10.1158/1078-0432.1129.11.3 · Cited by 117 · see citing works
Harnessing the hypoxia-inducible factor in cancer and ischemic disease
Brahimi-Horn, M. C., & Pouysségur, J. (2006) · Biochemical Pharmacology · doi:10.1016/j.bcp.2006.10.013 · Cited by 115 · see citing works
Hypoxia-inducible factor-1 in tumour angiogenesis
Shi, Y., & Fang, W. (2004) · World Journal of Gastroenterology · doi:10.3748/wjg.v10.i8.1082 · Cited by 114 · see citing works
Recent agents targeting HIF‐1α for cancer therapy
Hu, Y., Liu, J., & Huang, H. (2013) · Journal of Cellular Biochemistry · doi:10.1002/jcb.24390 · Cited by 113 · see citing works
Global phosphoproteomic effects of natural tyrosine kinase inhibitor, genistein, on signaling pathways
Yan, G., Xiao, C., He, G., Yin, X., Chen, N., Cao, Y., & He, Q. (2010) · PROTEOMICS · doi:10.1002/pmic.200900662 · Cited by 112 · see citing works
Simultaneous activation of several second messengers in hypoxia‐induced hyperpermeability of brain derived endothelial cells
Fischer, S., Wiesnet, M., Marti, H. H., Renz, D., & Schaper, W. K. A. (2003) · Journal of Cellular Physiology · doi:10.1002/jcp.10417 · Cited by 108 · see citing works
Histone Deacetylase Inhibitors Repress the Transactivation Potential of Hypoxia-inducible Factors Independently of Direct Acetylation of HIF-α
Fath, D. M., Kong, X., Liang, D., Lin, Z., Chou, A. D., Jiang, Y., Fang, J., Caro, J., & Sang, N. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m600456200 · Cited by 108 · see citing works
Self-citation
Proteasomal Inhibition Attenuates Transcriptional Activity of Hypoxia-Inducible Factor 1 (HIF-1) via Specific Effect on the HIF-1α C-Terminal Activation Domain
Kaluz, S., Kaluzová, M., & Stanbridge, E. J. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.00552-06 · Cited by 108 · see citing works
Targeting carbonic anhydrase IX and XII isoforms with small molecule inhibitors and monoclonal antibodies
Kciuk, M., Gielecińska, A., Mujwar, S., Mojzych, M., Marciniak, B., Drozda, R., & Kontek, R. (2022) · Journal of Enzyme Inhibition and Medicinal Chemistry · doi:10.1080/14756366.2022.2052868 · Cited by 107 · see citing works
In vitro study of HIF‐1 activation and VEGF release by bFGF in the T47D breast cancer cell line under normoxic conditions: involvement of PI‐3K/Akt and MEK1/ERK pathways
Shi, Y., Wang, Y., Bingle, L., Gong, L. H., Heng, W.-J., Li, Y., & Fang, W. (2005) · The Journal of Pathology · doi:10.1002/path.1734 · Cited by 105 · see citing works
HIF‐1α and HIF‐2α play a central role in stretch‐induced but not shear‐stress‐induced angiogenesis in rat skeletal muscle
Milkiewicz, M., Doyle, J. L., Fudalewski, T., Ispanovic, E., Aghasi, M., & Haas, T. L. (2007) · The Journal of Physiology · doi:10.1113/jphysiol.2007.136325 · Cited by 104 · see citing works
PI3K and ERK-Induced Rac1 Activation Mediates Hypoxia-Induced HIF-1α Expression in MCF-7 Breast Cancer Cells
Du, J., Xu, R., Hu, Z., Tian, Y., Zhu, Y., Gu, L., & Zhou, L. (2011) · PLoS ONE · doi:10.1371/journal.pone.0025213 · Cited by 103 · see citing works
Translational reprogramming marks adaptation to asparagine restriction in cancer
Pathria, G., Lee, J. S., Hasnis, E., Tandoc, K. V., Scott, D. A., Verma, S. K., Feng, Y., Larue, L., Sahu, A. D., Topisirović, I., et al. (2019) · Nature Cell Biology · doi:10.1038/s41556-019-0415-1 · Cited by 97 · see citing works
Hypoxia-induced and stress-specific changes in chromatin structure and function
Johnson, A. B., & Barton, M. C. (2007) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/j.mrfmmm.2006.10.007 · Cited by 100 · see citing works
Role for casein kinase 2 in the regulation of HIF‐1 activity
Mottet, D., Ruys, S. P. D., Demazy, C., Raes, M. J., & Michiels, C. (2005) · International Journal of Cancer · doi:10.1002/ijc.21268 · Cited by 99 · see citing works
Living on the Edge: ROS Homeostasis in Cancer Cells and Its Potential as a Therapeutic Target
Brandl, N., Seitz, R., Sendtner, N., Müller, M., & Gülow, K. (2025) · Antioxidants · doi:10.3390/antiox14081002 · Cited by 104 · see citing works
Atypical CRM1-dependent Nuclear Export Signal Mediates Regulation of Hypoxia-inducible Factor-1α by MAPK
Mylonis, I., Chachami, G., Paraskeva, E., & Simos, G. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m803081200 · Cited by 96 · see citing works
ERK1/2 Regulates Intracellular ATP Levels through α-Enolase Expression in Cardiomyocytes Exposed to Ischemic Hypoxia and Reoxygenation
Mizukami, Y., Iwamatsu, A., Aki, T., Kimura, M., Nakamura, K., Nao, T., Okusa, T., Matsuzaki, M., Yoshida, K., & Kobayashi, S. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m402299200 · Cited by 96 · see citing works
The role of calcium in hypoxia-induced signal transduction and gene expression
Seta, K. A., Yuan, Y., Spicer, Z., Lü, G., Bedard, J. E. J., Ferguson, T., Pathrose, P., Cole-Strauss, A., Kaufhold, A., & Millhorn, D. E. (2004) · Cell Calcium · doi:10.1016/j.ceca.2004.02.006 · Cited by 94 · see citing works
A Dialogue between the Hypoxia-Inducible Factor and the Tumor Microenvironment
Dayan, F., Mazure, N. M., Brahimi-Horn, M. C., & Pouysségur, J. (2008) · Cancer Microenvironment · doi:10.1007/s12307-008-0006-3 · Cited by 93 · see citing works
High Glucose Up-regulates ADAM17 through HIF-1α in Mesangial Cells
Li, R., Uttarwar, L., Gao, B., Charbonneau, M., Shi, Y., Chan, J. S. D., Dubois, C. M., & Krepinsky, J. C. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.651604 · Cited by 91 · see citing works
The Impact of Oxidative Stress and AKT Pathway on Cancer Cell Functions and Its Application to Natural Products
Shiau, J., Chuang, Y.-T., Tang, J., Yang, K., Chang, F., Hou, M., Yen, C., & Chang, H. (2022) · Antioxidants · doi:10.3390/antiox11091845 · Cited by 94 · see citing works
Interspecies comparison of neuroglobin, cytoglobin and myoglobin: Sequence evolution and candidate regulatory elements
Wystub, S., Ebner, B., Fuchs, C., Weich, B., Burmester, T., & Hankeln, T. (2004) · Cytogenetic and Genome Research · doi:10.1159/000078011 · Cited by 90 · see citing works
Involvement of PI3K and MAPK Signaling in bcl-2-induced Vascular Endothelial Growth Factor Expression in Melanoma Cells
Trisciuoglio, D., Iervolino, A., Zupi, G., & Bufalo, D. D. (2005) · Molecular Biology of the Cell · doi:10.1091/mbc.e04-12-1087 · Cited by 90 · see citing works
Natural Product-Based Inhibitors of Hypoxia-Inducible Factor-1 (HIF-1)
Nagle, D. G., & Zhou, Y. (2006) · Current Drug Targets · doi:10.2174/138945006776054979 · Cited by 88 · see citing works
PI3K/AKT regulates aggrecan gene expression by modulating Sox9 expression and activity in nucleus pulposus cells of the intervertebral disc
Cheng, C.-C., Uchiyama, Y., Hiyama, A., Gajghate, S., Shapiro, I. M., & Risbud, M. V. (2009) · Journal of Cellular Physiology · doi:10.1002/jcp.21904 · Cited by 88 · see citing works
ErbB2 Activation Upregulates Glutaminase 1 Expression Which Promotes Breast Cancer Cell Proliferation
Qie, S., Chu, C., Li, W., Wang, C., & Sang, N. (2013) · Journal of Cellular Biochemistry · doi:10.1002/jcb.24684 · Cited by 87 · see citing works
Self-citation
The Hypoxia-Inducible Factor and Tumor Progression Along the Angiogenic Pathway
Brahimi-Horn, M. C., & Pouysségur, J. (2004) · International review of cytology · doi:10.1016/s0074-7696(04)42004-x · Cited by 85 · see citing works
Effects of Histone Deacetylase Inhibitors on HIF-1
Liang, D., Kong, X., & Sang, N. (2006) · Cell Cycle · doi:10.4161/cc.5.21.3409 · Cited by 85 · see citing works
Self-citation
Oncological implications of hypoxia inducible factor-1α (HIF-1α) expression
O’Donnell, J. L., Joyce, M., Shannon, A. M., Harmey, J. H., Geraghty, J., & Bouchier‐Hayes, D. M. (2006) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2006.05.003 · Cited by 84 · see citing works

Two transactivation domains of hypoxia-inducible factor-1alpha regulated by the MEK-1/p42/p44 MAPK pathway.
Lee, E., Yim, S., Lee, S., & Park, H. (2002) · PubMed · Cited by 47 · see citing works
Two Transactivation Domains of Hypoxia-inducible Factor-1α Regulated by the MEK-1/p42/p44 MAPK Pathway
Lee, E., Yim, S., Lee, S., & Park, H. (2002) · Molecules and Cells · doi:10.1016/s1016-8478(23)15067-9 · Cited by 39 · see citing works
p42/p44 Mitogen-activated Protein Kinases Phosphorylate Hypoxia-inducible Factor 1α (HIF-1α) and Enhance the Transcriptional Activity of HIF-1
Richard, D. E., Berra, E., Gothié, E., Roux, D., & Pouysségur, J. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.46.32631 · Cited by 790 · see citing works
Mitogen-Activated Protein Kinase Kinase Inhibitor PD98059 Blocks thetrans-Activation but Not the Stabilization or DNA Binding Ability of Hypoxia-Inducible Factor-1α
Hur, E., Chang, K. Y., Lee, E., Lee, S., & Park, H. (2001) · Molecular Pharmacology · doi:10.1124/mol.59.5.1216 · Cited by 111 · see citing works
Identification of MAPK Phosphorylation Sites and Their Role in the Localization and Activity of Hypoxia-inducible Factor-1α
Mylonis, I., Chachami, G., Samiotaki, M. K., Panayotou, G., Paraskeva, E., Kalousi, A., Georgatsou, E., Bonanou, S., & Simos, G. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m605058200 · Cited by 266 · see citing works

Authors: Sang, N., Stiehl, D. P., Bohensky, J., Leshchinsky, I., Srinivas, V., & Caro, J.
Affiliations: Thomas Jefferson University (US)
Corresponding author: Sang, Nianli
ORCID: Sang, Nianli
Stiehl, Daniel P.
Bohensky, Jolene
Venue: Journal of Biological Chemistry
Publisher: Elsevier BV
Published: 2003-04
Volume: 278
Issue: 16
Pages: 14013-14019
ISSN: 0021-9258 (ISSN-L)
DOI: 10.1074/jbc.m209702200
PMC: PMC4518846
OpenAlex: W2081329333
Cited by: 370
References: 55
Citations by year: 2026: 10 · 2025: 15 · 2024: 14 · 2023: 17 · 2022: 22 · 2021: 20 · 2020: 14 · 2019: 17 · 2018: 14 · 2017: 12 · 2016: 9 · 2015: 17 · 2014: 13 · 2013: 6 · 2012: 13
FWCI: 9.70
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
creativecommons.org/licenses/by/4.0/ (vor, 6475 d)
Locations: Journal of Biological Chemistry (publishedVersion, cc-by)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: American Heart Association
Johns Hopkins University
Temple University
University of Oxford
Boehringer Ingelheim Fonds
National Institutes of Health
National Heart, Lung, and Blood Institute (T32HL007821)
National Cancer Institute (R01CA089212, R01-CA89212, K01CA098809)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Kruppel-like factors research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
Keywords: hypoxia-inducible factor, HIF-1α, MAPK signaling, P300, CREB-binding protein, MEK1, transcriptional activation, transcriptional regulation, tumor hypoxia, oxygen sensing
MeSH terms: Endothelial PAS Domain-Containing Protein 1, Hypoxia, Cell Line, Dose-Response Relationship, Drug, Enzyme Activation, Glutathione Transferase, HeLa Cells, Humans, Luciferases, Models, Biological, Nuclear Proteins, Phosphorylation, Plasmids, Precipitin Tests, Protein Binding, Recombinant Fusion Proteins, Time Factors, Transcription Factors, Transfection, Blotting, Western, Signal Transduction, Transcriptional Activation, Trans-Activators, Up-Regulation, Protein Structure, Tertiary, MAP Kinase Signaling System, Basic Helix-Loop-Helix Transcription Factors, Basic Helix-Loop-Helix Proteins, Hypoxia-Inducible Factor 1, alpha Subunit

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

MAPK Signaling Up-regulates the Activity of Hypoxia-inducible Factors by Its Effects on p300

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Self-check

Cites

Cited by

Related

Record

About these checks