miR-605 joins p53 network to form a p53:miR-605:Mdm2 positive feedback loop in response to stress
Open accessAbstract
In cancers with wild-type (WT) p53 status, the function of p53 is inhibited through direct interaction with Mdm2 oncoprotein, a negative feedback loop to limit the function of p53. In response to cellular stress, p53 escapes the p53:Mdm2 negative feedback to accumulate rapidly to induce cell cycle arrest and apoptosis. We demonstrate herein that an microRNA miR-605 is a new component in the p53 gene network, being transcriptionally activated by p53 and post-transcriptionally repressing Mdm2. Activation of p53 upregulated miR-605 via interacting with the promoter region of the gene. Overexpression of miR-605 directly decreased Mdm2 expression at the post-transcriptional level but indirectly increased the transcriptional activity of p53 on miR-34a via downregulating Mdm2; knockdown of miR-605 did the opposite. Mdm2 inhibitor upregulated expression of both miR-34a and miR-605, which was mitigated by p53 inhibitor. miR-605 preferentially induced apoptosis in WT p53-expressing cells, an effect abolished by p53 inhibition. These results indicate that miR-605 acts to interrupt p53:Mdm2 interaction to create a positive feedback loop aiding rapid accumulation of p53 to facilitate its function in response to stress.
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miR-605 targets MDM2, triggering p53-mediated senescence.
“Conversely, miR-605 targets MDM2, triggering p53-mediated senescence (Xiao et al., 2011), and multiple miRNAs downregulate p21 WAF1/Cip1 , including 28 miRNAs that block OIS (Borgdorff et al., 2010).”
From Cellular Senescence: Defining a Path Forward (2019) · cites this paper as Xiao et al., 2011
The Mdm2-targeting section reports that miR-605 represses Mdm2, and the ‘Implication of miR-605 participation in the p53:Mdm2 signalling pathway’ section says this enhances p53 activity. That section links miR-605 to cell-cycle arrest or apoptosis, but does not establish that miR-605 triggers senescence specifically; it describes senescence as one possible form of p53-mediated arrest. Page numbers are unavailable in our copy. (LLM, conf=0.88)
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4 retracted
Xu, C., Lu, Y., Pan, Z., Chu, W., Luo, X., Lin, H., Xiao, J., Shan, H., Wang, Z., & Yang, B. (2007) · Journal of Cell Science · doi:10.1242/jcs.010728 · Cited by 439 · see citing works
Self-citationRetractedXiao, J., Luo, X., Lin, H., Zhang, Y., Lu, Y., Wang, N., Zhang, Y., Yang, B., & Wang, Z. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.c700015200 · Cited by 234 · see citing works
Self-citationRetractedLuo, X., Lin, H., Pan, Z., Xiao, J., Zhang, Y., Lu, Y., Yang, B., & Wang, Z. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m801035200 · Cited by 177 · see citing works
Self-citationRetractedLin, H., Xiao, J., Luo, X., Wang, H., Gao, H., Yang, B., & Wang, Z. (2007) · Journal of Cellular Physiology · doi:10.1002/jcp.21015 · Cited by 33 · see citing works
Self-citationRetractedMdm2 promotes the rapid degradation of p53
Haupt, Y., Maya, R., Kazaz, A., & Oren, M. (1997) · Nature · doi:10.1038/387296a0 · Cited by 4,506 · see citing works
Regulation of p53 stability by Mdm2
Kubbutat, M. H. G., Jones, S. N., & Vousden, K. H. (1997) · Nature · doi:10.1038/387299a0 · Cited by 3,312 · see citing works
Momand, J., Zambetti, G. P., Olson, D. C., George, D., & Levine, A. J. (1992) · Cell · doi:10.1016/0092-8674(92)90644-r · Cited by 3,113 · see citing works
Requirement for p53 and p21 to Sustain G <sub>2</sub> Arrest After DNA Damage
Bunz, F., Dutriaux, A., Lengauer, C., Waldman, T., Zhou, S., Brown, J. P., Sedivy, J. M., Kinzler, K. W., & Vogelstein, B. (1998) · Science · doi:10.1126/science.282.5393.1497 · Cited by 2,803 · see citing works
A microRNA component of the p53 tumour suppressor network
He, L., He, X., Lim, L. P., de Stanchina, E., Xuan, Z., Liang, Y., Xue, W., Zender, L., Magnus, J., Ridzon, D., et al. (2007) · Nature · doi:10.1038/nature05939 · Cited by 2,692 · see citing works
Transactivation of miR-34a by p53 broadly influences gene expression and promotes apoptosis
Chang, T.-C., Wentzel, E. A., Kent, O. A., Ramachandran, K., Mullendore, M., Lee, K. H., Feldmann, G., Yamakuchi, M., Ferlito, M., Lowenstein, C. J., et al. (2007) · Molecular Cell · doi:10.1016/j.molcel.2007.05.010 · Cited by 2,010 · see citing works
The p53 pathway: positive and negative feedback loops
Harris, S. L., & Levine, A. J. (2005) · Oncogene · doi:10.1038/sj.onc.1208615 · Cited by 1,967 · see citing works
Oncoprotein MDM2 is a ubiquitin ligase E3 for tumor suppressor p53
Honda, R., Tanaka, H., & Yasuda, H. (1997) · FEBS Letters · doi:10.1016/s0014-5793(97)01480-4 · Cited by 1,951 · see citing works
Transcriptional Activation of miR-34a Contributes to p53-Mediated Apoptosis
Raver-Shapira, N., Marciano, E., Meiri, E., Spector, Y., Rosenfeld, N., Moskovits, N. B.-C., Bentwich, Z., & Oren, M. (2007) · Molecular Cell · doi:10.1016/j.molcel.2007.05.017 · Cited by 1,352 · see citing works
mdm2 expression is induced by wild type p53 activity.
Barak, Y., Juven, T., Haffner, R., & Oren, M. (1993) · The EMBO Journal · doi:10.1002/j.1460-2075.1993.tb05678.x · Cited by 1,290 · see citing works
The miR-34 family in cancer and apoptosis
Hermeking, H. (2010) · Cell Death & Differentiation · doi:10.1038/cdd.2009.56 · Cited by 1,236 · see citing works
Yang, B., Lin, H., Xiao, J., Lu, Y., Luo, X., Li, B., Zhang, Y., Xu, C., Bai, Y., Wang, H., et al. (2007) · Nature Medicine · doi:10.1038/nm1569 · Cited by 1,140 · see citing works
Self-citationTarasov, V., Jung, P., Verdoodt, B., Lodygin, D., Epanchintsev, A., Menssen, A., Meister, G., & Hermeking, H. (2007) · Cell Cycle · doi:10.4161/cc.6.13.4436 · Cited by 922 · see citing works
MicroRNA-34a functions as a potential tumor suppressor by inducing apoptosis in neuroblastoma cells
Welch, C., Chen, Y., & Stallings, R. L. (2007) · Oncogene · doi:10.1038/sj.onc.1210293 · Cited by 805 · see citing works
Relevance of Breast Cancer Cell Lines as Models for Breast Tumours: An Update
Lacroix, M., & Leclercq, G. (2004) · Breast Cancer Research and Treatment · doi:10.1023/b:brea.0000014042.54925.cc · Cited by 784 · see citing works
Shangary, S., & Wang, S. (2009) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.48.113006.094723 · Cited by 623 · see citing works
Morishita, R., Sugimoto, T., Aoki, M., Kida, I., Tomita, N., Moriguchi, A., Maeda, K., Sawa, Y., Kaneda, Y., Higaki, J., et al. (1997) · Nature Medicine · doi:10.1038/nm0897-894 · Cited by 584 · see citing works
MDM2 inhibitors for cancer therapy
Vassilev, L. T. (2007) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2006.11.002 · Cited by 532 · see citing works
New class of microRNA targets containing simultaneous 5′-UTR and 3′-UTR interaction sitesPreprint
Lee, I., Ajay, S. S., Yook, J. I., Kim, H. S., Hong, S. H., Kim, N. H., Dhanasekaran, S. M., Chinnaiyan, A. M., & Athey, B. D. (2009) · Genome Research · doi:10.1101/gr.089367.108 · Cited by 485 · see citing works
The p53 orchestra: Mdm2 and Mdmx set the tone
Wade, M., Wang, Y. V., & Wahl, G. M. (2010) · Trends in Cell Biology · doi:10.1016/j.tcb.2010.01.009 · Cited by 450 · see citing works
(2002) · PubMed · Cited by 228 · see citing works
MicroRNA-34 mediates AR-dependent p53-induced apoptosis in prostate cancer
Rokhlin, O. W., Scheinker, V., Taghiyev, A. F., Bumcrot, D. A., Glover, R. A., & Cohen, M. B. (2008) · Cancer Biology & Therapy · doi:10.4161/cbt.7.8.6284 · Cited by 159 · see citing works
Lu, Y., Xiao, J., Lin, H., Bai, Y., Luo, X., Wang, Z., & Yang, B. (2009) · Nucleic Acids Research · doi:10.1093/nar/gkn1053 · Cited by 150 · see citing works
Self-citationEricson, K., Gan, C. M., Cheong, I., Rago, C., Samuels, Y., Velculescu, V. E., Kinzler, K. W., Huso, D. L., Vogelstein, B., & Papadopoulos, N. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0914018107 · Cited by 122 · see citing works
Small-molecule inhibitors of MDM2 as new anticancer therapeutics
Dickens, M. P., Fitzgerald, R. P., & Fischer, P. M. (2009) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2009.10.003 · Cited by 86 · see citing works
Oxidative Preconditioning and Apoptosis in L-cells
Han, H. J., Wang, H., Long, H., Nattel, S., & Wang, Z. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m011136200 · Cited by 79 · see citing works
Self-citationPatented inhibitors of p53–Mdm2 interaction (2006 – 2008)
Weber, L. (2010) · Expert Opinion on Therapeutic Patents · doi:10.1517/13543770903514129 · Cited by 45 · see citing works
p53 and MDM2: Antagonists or Partners in Crime?
Eischen, C. M., & Lozano, G. (2009) · Cancer Cell · doi:10.1016/j.ccr.2009.02.004 · Cited by 43 · see citing works
Gao, H., Xiao, J., Sun, Q., Lin, H., Bai, Y., Yang, L., Yang, B., Wang, H., & Wang, Z. (2006) · Molecular Pharmacology · doi:10.1124/mol.106.024273 · Cited by 43 · see citing works
Self-citationKeimling, M., & Wiesmüller, L. (2009) · Carcinogenesis · doi:10.1093/carcin/bgp117 · Cited by 32 · see citing works
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Cellular Senescence: Defining a Path Forward
Gorgoulis, V., Adams, P. D., Alimonti, A., Bennett, D. C., Bischof, O., Bishop, C., Campisi, J., Collado, M., Evangelou, K., Ferbeyre, G., et al. (2019) · Cell · doi:10.1016/j.cell.2019.10.005 · Cited by 3,225 · see citing works
Mechanisms of Cellular Senescence: Cell Cycle Arrest and Senescence Associated Secretory Phenotype
Kumari, R., & Jat, P. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.645593 · Cited by 1,622 · see citing works
Lujambio, A., & Lowe, S. W. (2012) · Nature · doi:10.1038/nature10888 · Cited by 1,084 · see citing works
MicroRNAs in the p53 network: micromanagement of tumour suppression
Hermeking, H. (2012) · Nature Reviews Cancer · doi:10.1038/nrc3318 · Cited by 518 · see citing works
The role of ubiquitin modification in the regulation of p53
Hock, A. K., & Vousden, K. H. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2013.05.022 · Cited by 168 · see citing works
Arcila, M. L., Betizeau, M., Cambronne, X. A., Guzman, E., Doerflinger, N., Bouhallier, F., Zhou, H., Wu, B., Rani, N., Bassett, D. S., et al. (2014) · Neuron · doi:10.1016/j.neuron.2014.01.017 · Cited by 80 · see citing works
MicroRNA controls of cellular senescence
Suh, N. (2018) · BMB Reports · doi:10.5483/bmbrep.2018.51.10.209 · Cited by 78 · see citing works
Herman, A. B., Anerillas, C., Harris, S. C., Munk, R., Martindale, J. L., Yang, X., Mazan-Mamczarz, K., Zhang, Y., Heckenbach, I. J., Scheibye-Knudsen, M., et al. (2021) · Nucleic Acids Research · doi:10.1093/nar/gkab538 · Cited by 31 · see citing works
- Authors
- Xiao, J., Lin, H., Luo, X., Luo, X., & Wang, Z.
- Affiliations
- Montreal Heart Institute (CA)
- Corresponding author
- Xiao, Jiening
- Wang, Zhiguo
- Venue
- The EMBO Journal
- Published
- 2011-01-07
- Volume
- 30
- Issue
- 3
- Pages
- 524-532
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC3034018
- OpenAlex
- W2159266275
- Cited by
- 189
- References
- 34
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 7 · 2023: 7 · 2022: 15 · 2021: 10 · 2020: 11 · 2019: 16 · 2018: 14 · 2017: 12 · 2016: 9 · 2015: 12 · 2014: 22 · 2013: 15 · 2012: 21
- FWCI
- 10.54
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- The EMBO Journal (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Canadian Institutes of Health Research
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
- Keywords
- p53, MDM2, positive feedback loop, p53-MDM2 interaction, miR-34a, cellular stress response, apoptosis, post-transcriptional regulation, transcriptional activation, MDM2 inhibitors
- MeSH terms
- Analysis of Variance, Enzyme-Linked Immunosorbent Assay, Female, Gene Expression Regulation, Humans, Luciferases, Plasmids, Stress, Physiological, Tetrazolium Salts, Thiazoles, Blotting, Western, Tumor Suppressor Protein p53, Apoptosis, Cyclic GMP-Dependent Protein Kinases, Reverse Transcriptase Polymerase Chain Reaction, In Situ Nick-End Labeling, Electrophoretic Mobility Shift Assay, Feedback, Physiological, MicroRNAs, Cell Line, Tumor, Chromatin Immunoprecipitation, Proto-Oncogene Proteins c-mdm2, Caspase 3, Cyclic GMP-Dependent Protein Kinase Type I
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