The unfolded protein response and cellular senescence. A Review in the Theme: Cellular Mechanisms of Endoplasmic Reticulum Stress Signaling in Health and Disease

The Hallmarks of Aging

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A biomarker that identifies senescent human cells in culture and in aging skin in vivo.

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Signal integration in the endoplasmic reticulum unfolded protein response

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The limited in vitro lifetime of human diploid cell strains

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Telomeres shorten during ageing of human fibroblasts

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Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a

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XBP1 mRNA Is Induced by ATF6 and Spliced by IRE1 in Response to ER Stress to Produce a Highly Active Transcription Factor

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Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders

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An Integrated Stress Response Regulates Amino Acid Metabolism and Resistance to Oxidative Stress

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THE MAMMALIAN UNFOLDED PROTEIN RESPONSE

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Coupling of Stress in the ER to Activation of JNK Protein Kinases by Transmembrane Protein Kinase IRE1

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IRE1 couples endoplasmic reticulum load to secretory capacity by processing the XBP-1 mRNA

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Intracellular Functions of N-Linked Glycans

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Cellular response to oxidative stress: Signaling for suicide and survival *

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Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors

Campisi, J. (2005) · Cell · doi:10.1016/j.cell.2005.02.003 · Cited by 2,359 · cited 3× · see citing works

Mediators of endoplasmic reticulum stress-induced apoptosis

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Rb-mediated heterochromatin formation and silencing of E2F target genes during cellular senescence

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Stress signaling from the lumen of the endoplasmic reticulum: coordination of gene transcriptional and translational controlsPreprint

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BRAFE600-associated senescence-like cell cycle arrest of human naevi

Michaloglou, C., Vredeveld, L. C. W., Soengas, M. S., Denoyelle, C., Kuilman, T., van der Horst, C. M. A. M., Majoor, D. M., Shay, J. W., Mooi, W. J., & Peeper, D. S. (2005) · Nature · doi:10.1038/nature03890 · Cited by 2,160 · see citing works

The essence of senescence: Figure 1.

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Autophagy Is Activated for Cell Survival after Endoplasmic ReticulumStress

Ogata, M., Hino, S.-I., Saito, A., Morikawa, K., Kondo, S., Kanemoto, S., Murakami, T., Taniguchi, M., Tanii, I., Yoshinaga, K., et al. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.01453-06 · Cited by 1,832 · see citing works

Senescent fibroblasts promote epithelial cell growth and tumorigenesis: A link between cancer and aging

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Senescence in premalignant tumours

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Plasma cell differentiation requires the transcription factor XBP-1

Reimold, A., Iwakoshi, N., Manis, J., Vallabhajosyula, P., Szomolanyi-Tsuda, E., Gravallese, E., Friend, D., Grusby, M., Alt, F., & Glimcher, L. (2001) · Nature · doi:10.1038/35085509 · Cited by 1,371 · see citing works

Decay of Endoplasmic Reticulum-Localized mRNAs During the Unfolded Protein Response

Hollien, J., & Weissman, J. S. (2006) · Science · doi:10.1126/science.1129631 · Cited by 1,319 · see citing works

Nrf2 Is a Direct PERK Substrate and Effector of PERK-Dependent Cell Survival

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Senescence is a developmental mechanism that contributes to embryonic growth and patterning

Storer, M., Mas, A., Robert-Moreno, A., Pecoraro, M., Ortells, M. C., Di Giacomo, V., Yosef, R., Pilpel, N., Krizhanovsky, V., Sharpe, J., et al. (2013) · Cell · doi:10.1016/j.cell.2013.10.041 · Cited by 1,186 · see citing works

Living on a break: cellular senescence as a DNA-damage response

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Proteasome inhibitors induce a terminal unfolded protein response in multiple myeloma cells

Obeng, E. A., Carlson, L. M., Gutman, D. M., Harrington, W. J., Lee, K. P., & Boise, L. (2006) · Blood · doi:10.1182/blood-2005-08-3531 · Cited by 1,147 · see citing works

Senescence in tumours: evidence from mice and humans

Collado, M., & Serrano, M. (2010) · Nature Reviews Cancer · doi:10.1038/nrc2772 · Cited by 1,124 · see citing works

Fat tissue, aging, and cellular senescence

Tchkonia, T., Morbeck, D. E., Von Zglinicki, T., Van Deursen, J., Lustgarten, J., Scrable, H., Khosla, S., Jensen, M. D., & Kirkland, J. L. (2010) · Aging Cell · doi:10.1111/j.1474-9726.2010.00608.x · Cited by 1,094 · see citing works

ER stress and diseases

Yoshida, H. (2007) · The FEBS Journal · doi:10.1111/j.1742-4658.2007.05639.x · Cited by 1,086 · see citing works

Autophagy mediates the mitotic senescence transition

Young, A. R. J., Narita, M., Ferreira, M., Kirschner, K., Sadaie, M., Darot, J. F. J., Tavaré, S., Arakawa, S., Shimizu, S., Watt, F. M., et al. (2009) · Genes & Development · doi:10.1101/gad.519709 · Cited by 1,078 · see citing works

XBP1, Downstream of Blimp-1, Expands the Secretory Apparatus and Other Organelles, and Increases Protein Synthesis in Plasma Cell Differentiation

Shaffer, A. L., Shelef, M. A., Iwakoshi, N. N., Lee, A., Qian, S., Zhao, H., Yu, X., Yang, L., Tan, B. K., Rosenwald, A., et al. (2004) · Immunity · doi:10.1016/j.immuni.2004.06.010 · Cited by 1,060 · see citing works

IRE1-mediated unconventional mRNA splicing and S2P-mediated ATF6 cleavage merge to regulate XBP1 in signaling the unfolded protein responsePreprint

Lee, K., Tirasophon, W., Shen, X., Michalak, M., Prywes, R., Okada, T., Yoshida, H., Mori, K., & Kaufman, R. J. (2002) · Genes & Development · doi:10.1101/gad.964702 · Cited by 1,055 · see citing works

The signals and pathways activating cellular senescence

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Oxidative protein folding in eukaryotes

Tu, B. P., & Weissman, J. S. (2004) · The Journal of Cell Biology · doi:10.1083/jcb.200311055 · Cited by 1,041 · see citing works

Regulated Ire1-dependent decay of messenger RNAs in mammalian cells

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Autophagy Counterbalances Endoplasmic Reticulum Expansion during the Unfolded Protein Response

Bernales, S., McDonald, K. L., & Walter, P. (2006) · PLoS Biology · doi:10.1371/journal.pbio.0040423 · Cited by 1,009 · see citing works

ER stress (PERK/eIF2α phosphorylation) mediates the polyglutamine-induced LC3 conversion, an essential step for autophagy formation

Kouroku, Y., Fujita, E., Tanida, I., Ueno, T., Isoai, A., Kumagai, H., Ogawa, S., Kaufman, R. J., Kominami, E., & Momoi, T. (2007) · Cell Death & Differentiation · doi:10.1038/sj.cdd.4401984 · Cited by 934 · see citing works

Mild hyperoxia shortens telomeres and inhibits proliferation of fibroblasts: a model for senescence?

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Cellular senescence and its effector programs

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Telomeric DNA damage is irreparable and causes persistent DNA-damage-response activation

Fumagalli, M., Rossiello, F., Clerici, M., Barozzi, S., Cittaro, D., Kaplunov, J. M., Bucci, G., Dobreva, M., Matti, V., Beausejour, C. M., et al. (2012) · Nature Cell Biology · doi:10.1038/ncb2466 · Cited by 851 · see citing works

The unfolded protein response protects human tumor cells during hypoxia through regulation of the autophagy genes MAP1LC3B and ATG5

Rouschop, K. M. A., van den Beucken, T., Dubois, L., Niessen, H., Bussink, J., Savelkouls, K., Keulers, T., Mujcic, H., Landuyt, W., Voncken, J. W., et al. (2010) · Journal of Clinical Investigation · doi:10.1172/jci40027 · Cited by 829 · see citing works

Microarray analysis of replicative senescence

Shelton, D. N., Chang, E., Whittier, P. S., Choi, D., & Funk, W. D. (1999) · Current Biology · doi:10.1016/s0960-9822(99)80420-5 · Cited by 764 · see citing works

Emerging role of NF-κB signaling in the induction of senescence-associated secretory phenotype (SASP)

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Cellular and molecular mechanisms of stress-induced premature senescence (SIPS) of human diploid fibroblasts and melanocytes

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DNA damage response and cellular senescence in tissues of aging mice

Wang, C., Jurk, D., Maddick, M., Nelson, G., Martin‐Ruiz, C., & Von Zglinicki, T. (2009) · Aging Cell · doi:10.1111/j.1474-9726.2009.00481.x · Cited by 696 · see citing works

ATF6α Optimizes Long-Term Endoplasmic Reticulum Function to Protect Cells from Chronic Stress

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ER-associated degradation: Protein quality control and beyond

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ATF4-dependent transcription mediates signaling of amino acid limitation

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Stress-Independent Activation of XBP1s and/or ATF6 Reveals Three Functionally Diverse ER Proteostasis Environments

Shoulders, M. D., Ryno, L. M., Genereux, J. C., Moresco, J. J., Tu, P. G., Wu, C., Yates, J. R., Su, A. I., Kelly, J. W., & Wiseman, R. L. (2013) · Cell Reports · doi:10.1016/j.celrep.2013.03.024 · Cited by 558 · see citing works

Synthetic lethal metabolic targeting of cellular senescence in cancer therapy

Dörr, J. R., Yu, Y., Milanovic, M., Beuster, G., Zasada, C., Däbritz, J. H. M., Lisec, J., Lenze, D., Gerhardt, A., Schleicher, K., et al. (2013) · Nature · doi:10.1038/nature12437 · Cited by 541 · see citing works

A negative feedback signaling network underlies oncogene-induced senescence

Courtois-Cox, S., Genther Williams, S. M., Reczek, E. E., Johnson, B. W., McGillicuddy, L. T., Johannessen, C. M., Hollstein, P. E., MacCollin, M., & Cichowski, K. (2006) · Cancer Cell · doi:10.1016/j.ccr.2006.10.003 · Cited by 501 · see citing works

Untitled work

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Endoplasmic Reticulum Stress in Malignancy

Clarke, H. J., Chambers, J. E., Liniker, E., & Marciniak, S. J. (2014) · Cancer Cell · doi:10.1016/j.ccr.2014.03.015 · Cited by 461 · see citing works

Integrated Endoplasmic Reticulum Stress Responses in Cancer

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The FAD- and O2-Dependent Reaction Cycle of Ero1-Mediated Oxidative Protein Folding in the Endoplasmic Reticulum

Tu, B. P., & Weissman, J. S. (2002) · Molecular Cell · doi:10.1016/s1097-2765(02)00696-2 · Cited by 433 · see citing works

Cellular senescence: a link between cancer and age-related degenerative disease?

Campisi, J., Andersen, J. K., Kapahi, P., & Melov, S. (2011) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2011.09.001 · Cited by 421 · see citing works

Mitochondrial Dysfunction Contributes to Oncogene-Induced Senescence

Moiseeva, O., Bourdeau, V., Roux, A., Deschênes-Simard, X., & Ferbeyre, G. (2009) · Molecular and Cellular Biology · doi:10.1128/mcb.01868-08 · Cited by 408 · cited 1× · see citing works

Cellular senescence is an important mechanism of tumor regression upon c-Myc inactivation

Wu, C.-H., van Riggelen, J., Yetil, A., Fan, A. C., Bachireddy, P., & Felsher, D. W. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0701953104 · Cited by 405 · see citing works

Stress management at the ER: Regulators of ER stress-induced apoptosis

Gorman, A. M., Healy, S., Jäger, R., & Afshin Samali, A. (2012) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2012.02.003 · Cited by 404 · see citing works

Skp2 targeting suppresses tumorigenesis by Arf-p53-independent cellular senescence

Lin, H.-K., Chen, Z., Wang, G., Nardella, C., Lee, S.-W., Chan, C.-H., Yang, W.-L., Wang, J., Egia, A., Nakayama, K. I., et al. (2010) · Nature · doi:10.1038/nature08815 · Cited by 400 · see citing works

The endoplasmic reticulum stress response in aging and age-related diseases

Brown, M. K., & Naidoo, N. N. (2012) · Frontiers in Physiology · doi:10.3389/fphys.2012.00263 · Cited by 372 · see citing works

Oncogene-Induced Cell Senescence — Halting on the Road to Cancer

Mooi, W. J., & Peeper, D. S. (2006) · New England Journal of Medicine · doi:10.1056/nejmra062285 · Cited by 371 · see citing works

Anti-oncogenic role of the endoplasmic reticulum differentially activated by mutations in the MAPK pathway

Denoyelle, C., Abou-Rjaily, G., Bezrookove, V., Verhaegen, M., Johnson, T. M., Fullen, D. R., Pointer, J. N., Gruber, S. B., Su, L. D., Nikiforov, M. A., et al. (2006) · Nature Cell Biology · doi:10.1038/ncb1471 · Cited by 349 · see citing works

The unfolded protein response sensor IRE1α is required at 2 distinct steps in B cell lymphopoiesis

Zhang, K., Wong, H. N., Song, B., Miller, C. N., Scheuner, D. L., & Kaufman, R. J. (2005) · Journal of Clinical Investigation · doi:10.1172/jci21848 · Cited by 348 · see citing works

Oncogene-induced reactive oxygen species fuel hyperproliferation and DNA damage response activation

Ogrunc, M., Di Micco, R., Liontos, M., Bombardelli, L., Mione, M., Fumagalli, M., Gorgoulis, V. G., & d'Adda di Fagagna, F. (2014) · Cell Death & Differentiation · doi:10.1038/cdd.2014.16 · Cited by 328 · see citing works

Activation of an Unfolded Protein Response during Differentiation of Antibody-secreting B Cells

Gass, J. N., Gifford, N. M., & Brewer, J. W. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m205011200 · Cited by 306 · see citing works

Senescence-Associated Secretory Phenotypes Reveal Cell-Nonautonomous Functions of Oncogenic RAS and the p53 Tumor Suppressor

Coppé, J.-P., Patil, C. K., Rodier, F., Sun, Y., Muñoz, D. P., Goldstein, J., Nelson, P. S., Desprez, P.-Y., & Campisi, J. (2008) · PLoS Biology · doi:10.1371/journal.pbio.0060301 · Cited by 302 · cited 2× · see citing works

ATF6α induces XBP1-independent expansion of the endoplasmic reticulum

Bommiasamy, H., Back, S. H., Fagone, P., Lee, K., Meshinchi, S., Vink, E. I., Sriburi, R., Frank, M. W., Jackowski, S., Kaufman, R. J., et al. (2009) · Journal of Cell Science · doi:10.1242/jcs.045625 · Cited by 299 · see citing works

Emerging roles of the p38 MAPK and PI3K/AKT/mTOR pathways in oncogene-induced senescence

Xu, Y., Li, N., Xiang, R., & Sun, P. (2014) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2014.04.004 · Cited by 282 · see citing works

Cellular senescence and the aging brain

Chinta, S. J., Woods, G., Rane, A., Demaria, M., Campisi, J., & Andersen, J. K. (2015) · Experimental Gerontology · doi:10.1016/j.exger.2014.09.018 · Cited by 282 · see citing works

ER and aging—Protein folding and the ER stress response

Naidoo, N. N. (2009) · Ageing Research Reviews · doi:10.1016/j.arr.2009.03.001 · Cited by 280 · see citing works

Replicative senescence: a critical review

Cristofalo, V. J., Lorenzini, A., Allen, R. G., Torres, C. A., & Tresini, M. (2004) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2004.07.010 · Cited by 275 · see citing works

Senescent cells develop a parp-1 and nuclear factor-κB-associated secretome (PNAS).

Ohanna, M., Giuliano, S., Bonet, C., Imbert, V., Hofman, V., Zangari, J., Bille, K., Robert, C., Bressac-de Paillerets, B., Hofman, P., et al. (2011) · Genes & Development · doi:10.1101/gad.625811 · Cited by 267 · see citing works

Coordinate Regulation of Phospholipid Biosynthesis and Secretory Pathway Gene Expression in XBP-1(S)-induced Endoplasmic Reticulum Biogenesis

Sriburi, R., Bommiasamy, H., Buldak, G. L., Robbins, G. R., Frank, M. W., Jackowski, S., & Brewer, J. W. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m609490200 · Cited by 262 · see citing works

Metabolic analysis of senescent human fibroblasts reveals a role for AMP in cellular senescence

Zwerschke, W., Mazurek, S., Stöckl, P., Hütter, E., EIGENBRODT, E., & Jansen‐Dürr, P. (2003) · Biochemical Journal · doi:10.1042/bj20030816 · Cited by 248 · see citing works

Apoptosis in Proliferating, Senescent, and Immortalized Keratinocytes

Chaturvedi, V., Qin, J., Denning, M. F., Choubey, D., Dı́az, M. O., & Nickoloff, B. J. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.33.23358 · Cited by 213 · see citing works

Interaction between ROS dependent DNA damage, mitochondria and p38 MAPK underlies senescence of human adult stem cells

Borodkina, A. V., Shatrova, A. N., Abushik, P. A., Nikolsky, N. N., & Burova, E. (2014) · Aging · doi:10.18632/aging.100673 · Cited by 205 · see citing works

Oleate Blocks Palmitate-Induced Abnormal Lipid Distribution, Endoplasmic Reticulum Expansion and Stress, and Insulin Resistance in Skeletal Muscle

Gong, P., Li, L., Liu, Y., Pu, J., Zhang, S., Yu, J., Zhao, J., & Liu, P. (2011) · Endocrinology · doi:10.1210/en.2010-1369 · Cited by 199 · see citing works

Structure-Based Design and Evaluation of Naphthalene Diimide G-Quadruplex Ligands As Telomere Targeting Agents in Pancreatic Cancer Cells

Micco, M., Collie, G. W., Dale, A. G., Ohnmacht, S. A., Pazitna, I., Gunaratnam, M., Reszka, A. P., & Neidle, S. (2013) · Journal of Medicinal Chemistry · doi:10.1021/jm301899y · Cited by 184 · see citing works

Receptor for advanced glycation end-products promotes premature senescence of proximal tubular epithelial cells via activation of endoplasmic reticulum stress-dependent p21 signaling

Liu, J., Huang, K., Cai, G.-Y., Chen, X.-M., Yang, J.-R., Lin, L.-R., Yang, J., Huo, B.-G., Zhan, J., & He, Y.-N. (2014) · Cellular Signalling · doi:10.1016/j.cellsig.2013.10.002 · Cited by 181 · see citing works

Redox signaling loops in the unfolded protein response

Higa, A., & Chevet, É. (2012) · Cellular Signalling · doi:10.1016/j.cellsig.2012.03.011 · Cited by 174 · see citing works

Virus-induced ER stress and the unfolded protein response

Zhang, L., & Wang, A. (2012) · Frontiers in Plant Science · doi:10.3389/fpls.2012.00293 · Cited by 168 · see citing works

Expression of catalytically active telomerase does not prevent premature senescence caused by overexpression of oncogenic Ha-Ras in normal human fibroblasts.

Wei, S., Wei, S., & Sedivy, J. M. (1999) · PubMed · Cited by 166 · see citing works

Definition of pRB- and p53-Dependent and -Independent Steps in HIRA/ASF1a-Mediated Formation of Senescence-Associated Heterochromatin Foci

Ye, X., Zerlanko, B. J., Zhang, R., Somaiah, N., Lipinski, M., Salomoni, P., & Adams, P. D. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.01592-06 · Cited by 161 · see citing works

Irreparable telomeric DNA damage and persistent DDR signalling as a shared causative mechanism of cellular senescence and ageing

Rossiello, F., Herbig, U., Longhese, M. P., Fumagalli, M., & di Fagagna, F. D. (2014) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2014.06.009 · Cited by 156 · see citing works

Carbonylation of ER chaperone proteins in aged mouse liver

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Transcriptional up-regulation of ULK1 by ATF4 contributes to cancer cell survival

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