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The Transcription Factor ATF4 Promotes Skeletal Myofiber Atrophy during Fasting
Open accessAbstract
Prolonged fasting alters skeletal muscle gene expression in a manner that promotes myofiber atrophy, but the underlying mechanisms are not fully understood. Here, we examined the potential role of activating transcription factor 4 (ATF4), a transcription factor with an evolutionarily ancient role in the cellular response to starvation. In mouse skeletal muscle, fasting increases the level of ATF4 mRNA. To determine whether increased ATF4 expression was required for myofiber atrophy, we reduced ATF4 expression with an inhibitory RNA targeting ATF4 and found that it reduced myofiber atrophy during fasting. Likewise, reducing the fasting level of ATF4 mRNA with a phosphorylation-resistant form of eukaryotic initiation factor 2alpha decreased myofiber atrophy. To determine whether ATF4 was sufficient to reduce myofiber size, we overexpressed ATF4 and found that it reduced myofiber size in the absence of fasting. In contrast, a transcriptionally inactive ATF4 construct did not reduce myofiber size, suggesting a requirement for ATF4-mediated transcriptional regulation. To begin to determine the mechanism of ATF4-mediated myofiber atrophy, we compared the effects of fasting and ATF4 overexpression on global skeletal muscle mRNA expression. Interestingly, expression of ATF4 increased a small subset of five fasting-responsive mRNAs, including four of the 15 mRNAs most highly induced by fasting. These five mRNAs encode proteins previously implicated in growth suppression (p21(Cip1/Waf1), GADD45alpha, and PW1/Peg3) or titin-based stress signaling [muscle LIM protein (MLP) and cardiac ankyrin repeat protein (CARP)]. Taken together, these data identify ATF4 as a novel mediator of skeletal myofiber atrophy during starvation.
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“Importantly, the overexpression of ATF4 and GADD45 is sufficient to induce muscle loss [19, 20].”
From The connection between the dynamic remodeling of the mitochondrial network and the regulation of muscle mass (2021) · cites this paper as [19]
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Cites
WAF1, a potential mediator of p53 tumor suppression
El-Deiry, W. S., Tokino, T., Velculescu, V. E., Levy, D. B., Parsons, R., Trent, J. M., Lin, D., Mercer, W. E., Kinzler, K. W., & Vogelstein, B. (1993) · Cell · doi:10.1016/0092-8674(93)90500-p · Cited by 8,321
The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases.
Wade Harper, J. (1993) · Cell · doi:10.1016/0092-8674(93)90499-g · Cited by 5,651
Identification of ubiquitin ligases required for skeletal muscle atrophy.
Bodine, S. C., Latres, E., Baumhueter, S., Lai, V. K.-M., Nunez, L., Clarke, B. A., Poueymirou, W. T., Panaro, F. J., Na, E., Dharmarajan, K., et al. (2001) · Science · doi:10.1126/science.1065874 · Cited by 3,521
An Integrated Stress Response Regulates Amino Acid Metabolism and Resistance to Oxidative Stress
Harding, H. P., Zhang, Y., Zeng, H., Novoa, I., Lu, P. D., Calfon, M. A., Sadri, N., Yun, C., Popko, B., Paules, R. S., et al. (2003) · Molecular Cell · doi:10.1016/s1097-2765(03)00105-9 · Cited by 3,336
Sandri, M., Sandri, C., Gilbert, A., Skurk, C., Calabria, E., Picard, A., Walsh, K., Schiaffino, S., Lecker, S. H., & Goldberg, A. L. (2004) · Cell · doi:10.1016/s0092-8674(04)00400-3 · Cited by 3,012
Bodine, S. C., Stitt, T. N., Gonzalez, M., Kline, W. O., Stover, G. L., Bauerlein, R., Zlotchenko, E., Scrimgeour, A., Lawrence, J. C., Glass, D. J., et al. (2001) · Nature Cell Biology · doi:10.1038/ncb1101-1014 · Cited by 2,752
FoxO3 Controls Autophagy in Skeletal Muscle In Vivo
Mammucari, C., Milan, G., Romanello, V., Masiero, E., Rudolf, R., Del Piccolo, P., Burden, S. J., Di Lisi, R., Sandri, C., Zhao, J., et al. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2007.11.001 · Cited by 1,953
TRANSLATIONAL REGULATION OFGCN4AND THE GENERAL AMINO ACID CONTROL OF YEAST
Hinnebusch, A. G. (2005) · Annual Review of Microbiology · doi:10.1146/annurev.micro.59.031805.133833 · Cited by 1,297
Sandri, M., Lin, J., Handschin, C., Yang, W., Arany, Z. P., Lecker, S. H., Goldberg, A. L., & Spiegelman, B. M. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0607795103 · Cited by 974
Signaling in Muscle Atrophy and Hypertrophy
Sandri, M. (2008) · Physiology · doi:10.1152/physiol.00041.2007 · Cited by 866
Knöll, R., Hoshijima, M., Hoffman, H. M., Person, V., Lorenzen-Schmidt, I., Bang, M.-L., Hayashi, T., Shiga, N., Yasukawa, H., Schaper, W., et al. (2002) · Cell · doi:10.1016/s0092-8674(02)01226-6 · Cited by 786
The E3 Ligase MuRF1 Degrades Myosin Heavy Chain Protein in Dexamethasone-Treated Skeletal Muscle
Clarke, B. A., Drujan, D., Willis, M. S., Murphy, L. O., Corpina, R. A., Burova, E., Rakhilin, S. V., Stitt, T. N., Patterson, C., Latres, E., et al. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2007.09.009 · Cited by 683
Granzier, H. L. M., & Labeit, S. (2004) · Circulation Research · doi:10.1161/01.res.0000117769.88862.f8 · Cited by 661
Cohen, S., Brault, J. J., Gygi, S. P., Glass, D. J., Valenzuela, D. M., Gartner, C. A., Latres, E., & Goldberg, A. L. (2009) · The Journal of Cell Biology · doi:10.1083/jcb.200901052 · Cited by 610
Sacheck, J. M., Hyatt, J. K., Raffaello, A., Thomas Jagoe, R., Roy, R. R., Reggie Edgerton, V., Lecker, S. H., & Goldberg, A. L. (2007) · The FASEB Journal · doi:10.1096/fj.06-6604com · Cited by 585
Skeletal Muscle Is a Primary Target of SOD1G93A-Mediated Toxicity
Dobrowolny, G., Aucello, M., Rizzuto, E., Beccafico, S., Mammucari, C., Bonconpagni, S., Belia, S., Wannenes, F., Nicoletti, C., Del Prete, Z., et al. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2008.09.002 · Cited by 513
Identification of Activating Transcription Factor 4 (ATF4) as an Nrf2-interacting Protein
He, C. H., Gong, P., Hu, B., Stewart, D., Choi, M. E., Choi, A. M. K., & Alam, J. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m101198200 · Cited by 472
Muscle LIM protein, a novel essential regulator of myogenesis, promotes myogenic differentiation
Arber, S. (1994) · Cell · doi:10.1016/0092-8674(94)90192-9 · Cited by 441
Pallafacchina, G., Calabria, E., Serrano, A. L., Kalhovde, J. M., & Schiaffino, S. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.142166599 · Cited by 402
Kaufman, R. J., Davies, M. V., Pathak, V. K., & Hershey, J. W. B. (1989) · Molecular and Cellular Biology · doi:10.1128/mcb.9.3.946-958.1989 · Cited by 395
eIF2 and the control of cell physiology
Proud, C. G. (2004) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2004.11.004 · Cited by 378
Gene expression profile of aging in human muscle
Welle, S. L., Brooks, A. I., Delehanty, J. M., Needler, N. A., & Thornton, C. A. (2003) · Physiological Genomics · doi:10.1152/physiolgenomics.00049.2003 · Cited by 364
Miller, M. K., Bang, M., Witt, C. C., Labeit, D., Trombitas, C., Watanabe, K., Granzier, H. L. M., McElhinny, A., Gregorio, C. C., & Labeit, S. (2003) · Journal of Molecular Biology · doi:10.1016/j.jmb.2003.09.012 · Cited by 356
Patterns of gene expression in atrophying skeletal muscles: response to food deprivation
Jagoe, R. T., Lecker, S. H., Gomes, M., & Goldberg, A. L. (2002) · The FASEB Journal · doi:10.1096/fj.02-0312com · Cited by 344
Lagirand-Cantaloube, J., Offner, N., Csibi, A., Leibovitch, M.-P., Batonnet‐Pichon, S., Tintignac, L. A. J., Segura, C. T., & Leibovitch, S. A. (2008) · The EMBO Journal · doi:10.1038/emboj.2008.52 · Cited by 344
Translational Control and the Unfolded Protein Response
Wek, R. C., & Cavener, D. R. (2007) · Antioxidants and Redox Signaling · doi:10.1089/ars.2007.1764 · Cited by 315
Judge, S. M., DODD, S. L., McClung, J. M., & Judge, A. R. (2008) · The FASEB Journal · doi:10.1096/fj.08-110163 · Cited by 289
Siu, F., Bain, P. J., LeBlanc-Chaffin, R., Chen, H., & Kilberg, M. S. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m201959200 · Cited by 278
CARP, a cardiac ankyrin repeat protein, is downstream in the Nkx2-5 homeobox gene pathway
Zou, Y., Evans, S. Μ., Chen, J., Kuo, H.-C., Harvey, R. P., & Chien, K. R. (1997) · Development · doi:10.1242/dev.124.4.793 · Cited by 277
Ras is involved in nerve-activity-dependent regulation of muscle genes
Murgia, M., Serrano, A. L., Calabria, E., Pallafacchina, G., Lømo, T., & Schiaffino, S. (2000) · Nature Cell Biology · doi:10.1038/35004013 · Cited by 218
Inhibition of Atrogin-1/MAFbx Mediated MyoD Proteolysis Prevents Skeletal Muscle Atrophy In Vivo
Lagirand-Cantaloube, J., Cornille, K., Csibi, A., Batonnet‐Pichon, S., Leibovitch, M.-P., & Leibovitch, S. A. (2009) · PLoS ONE · doi:10.1371/journal.pone.0004973 · Cited by 218
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Welle, S., Brooks, A. I., Delehanty, J. M., Needler, N., Bhatt, K., Shah, B., & Thornton, C. A. (2004) · Experimental Gerontology · doi:10.1016/j.exger.2003.11.011 · Cited by 210
Yamaguchi, S., Ishihara, H., Yamada, T., Tamura, A., Usui, M., Tominaga, R., Munakata, Y., Satake, C., Katagiri, H., Tashiro, F., et al. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2008.01.008 · Cited by 189
Gene expression profiling of aging reveals activation of a p53-mediated transcriptional program
Edwards, M. G., Anderson, R. M., Yuan, M., Kendziorski, C. M., Weindruch, R., & Prolla, T. A. (2007) · BMC Genomics · doi:10.1186/1471-2164-8-80 · Cited by 174
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Pathak, V. K., Schindler, D. G., & Hershey, J. W. B. (1988) · Molecular and Cellular Biology · doi:10.1128/mcb.8.2.993-995.1988 · Cited by 98
Al‐Zghoul, M. B., Gerrard, D. E., Watkins, B. A., & Hannon, K. (2003) · The FASEB Journal · doi:10.1096/fj.03-0293fje · Cited by 96
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Laure, L., Suel, L., Roudaut, C., Bourg, N., Ouali, A., Bartoli, M., Richard, I., & Danièle, N. (2008) · FEBS Journal · doi:10.1111/j.1742-4658.2008.06814.x · Cited by 75
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Eley, H. L., Skipworth, R. J. E., Deans, D. A. C., Fearon, K. C. H., & Tisdale, M. J. (2007) · British Journal of Cancer · doi:10.1038/sj.bjc.6604150 · Cited by 50
Free amino acid and glutathione concentrations in muscle during short-term starvation and refeeding
Hammarqvist, F., Andersson, K., Luo, J., & Wernerman, J. (2005) · Clinical Nutrition · doi:10.1016/j.clnu.2004.10.004 · Cited by 43
Coexpression after electroporation of plasmid mixtures into muscle in vivo
Rana, Z. A., Ekmark, M., & Gundersen, K. (2004) · Acta Physiologica Scandinavica · doi:10.1111/j.1365-201x.2004.01282.x · Cited by 37
Lehti, M., Silvennoinen, M., Kivelä, R., Kainulainen, H., & Komulainen, J. (2006) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00229.2006 · Cited by 28
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Metadata
- Authors
- Ebert, S. M., Monteys, A. M., Fox, D. K., Bongers, K. S., Shields, B. E., Malmberg, S. E., Davidson, B. L., Suneja, M., & Adams, C. M.
- Affiliations
- University of Iowa (US)
- Iowa City VA Medical Center (US)
- Corresponding author
- Suneja, Manish
- Adams, Christopher M.
- ORCID
- Venue
- Molecular Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2010-04
- Volume
- 24
- Issue
- 4
- Pages
- 790-799
- ISSN
- 0888-8809 (ISSN-L)
- 1944-9917
- PMC
- PMC2852358
- OpenAlex
- W1965629756
- Cited by
- 130
- References
- 53
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 10 · 2023: 5 · 2022: 13 · 2021: 8 · 2020: 13 · 2019: 8 · 2018: 8 · 2017: 9 · 2016: 8 · 2015: 12 · 2014: 6 · 2013: 6 · 2012: 8
- FWCI
- 2.34
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular Endocrinology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Veterans Affairs (I01 BX000976)
- National Institute of General Medical Sciences (T32GM073610, T32GM007337)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR059115)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Endoplasmic Reticulum Stress and Disease
- Health Sciences › Nursing › Nutrition and Dietetics › Muscle metabolism and nutrition
- Keywords
- ATF4, muscle fiber atrophy, skeletal muscle, fasting, starvation response, eIF2α phosphorylation, transcriptional regulation, muscle gene expression, p21, GADD45A, muscle LIM protein, cardiac ankyrin repeat protein, growth inhibition
- MeSH terms
- Animals, Fasting, Male, Mice, Inbred C57BL, Muscular Atrophy, RNA, Messenger, Polymerase Chain Reaction, Muscle, Skeletal, Oligonucleotide Array Sequence Analysis, Mice, Activating Transcription Factor 4
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