The DOI matches its Crossref record; 43 of the 43 references it cites were found in a registry or an index.
Foxo transcription factors induce the atrophy-related ubiquitin ligase atrogin-1 and cause skeletal muscle atrophy.
Open accessAbstract
Skeletal muscle atrophy is a debilitating response to fasting, disuse, cancer, and other systemic diseases. In atrophying muscles, the ubiquitin ligase, atrogin-1 (MAFbx), is dramatically induced, and this response is necessary for rapid atrophy. Here, we show that in cultured myotubes undergoing atrophy, the activity of the PI3K/AKT pathway decreases, leading to activation of Foxo transcription factors and atrogin-1 induction. IGF-1 treatment or AKT overexpression inhibits Foxo and atrogin-1 expression. Moreover, constitutively active Foxo3 acts on the atrogin-1 promoter to cause atrogin-1 transcription and dramatic atrophy of myotubes and muscle fibers. When Foxo activation is blocked by a dominant-negative construct in myotubes or by RNAi in mouse muscles in vivo, atrogin-1 induction during starvation and atrophy of myotubes induced by glucocorticoids are prevented. Thus, forkhead factor(s) play a critical role in the development of muscle atrophy, and inhibition of Foxo factors is an attractive approach to combat muscle wasting.
Overview
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
Cites
Statistics
Verification
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?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Two muscle-specific E3 ubiquitin ligases, muscle RING finger 1 (MuRF1, also known as TRIM63) and muscle atrophy F-Box (MAFbx, also known as atrogin-1 or FBXO32), are thought to be key regulators of proteasomal proteolysis in skeletal muscle, especially under atrophy-inducing conditions (Cai et al., 2004; Sandri et al., 2004; Stitt et al., 2004).”
From Proteasome dysfunction induces muscle growth defects and protein aggregation (2014) · cites this paper as Sandri et al., 2004
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Two muscle-specific E3 ubiquitin ligases, MuRF1 and Atrogin1, are thought to be key regulators of proteasomal proteolysis in skeletal muscle, especially under atrophy-inducing conditions (Cai et al., 2004; Sandri et al., 2004).”
From Inducible Rpt3, a Proteasome Component, Knockout in Adult Skeletal Muscle Results in Muscle Atrophy (2020) · cites this paper as Sandri et al., 2004
Experimental — accuracy not yet measuredIn the citing paper
“Atrogin-1 plays a key role in muscle atrophy as muscle specific ubiquitin ligase.”
From GLP-1RA Liraglutide and Semaglutide Improves Obesity-Induced Muscle Atrophy via SIRT1 Pathway (2023) · cites this paper as [48]
In the citing paper
“FoxO family of transcription factors (FoxO1, FoxO3, and FoxO4) are critical mediators of the catabolic response during atrophy [9, 15, 16].”
From The connection between the dynamic remodeling of the mitochondrial network and the regulation of muscle mass (2021) · cites this paper as [9]
In the citing paper
“The IGF1–AKT-–mTOR axis increases protein synthesis by stimulating the translational machinery and simultaneously blocks FoxOs transcription factors and protein degradation [9].”
From The connection between the dynamic remodeling of the mitochondrial network and the regulation of muscle mass (2021) · cites this paper as [9]
In the citing paper
“Alterations in mPTP function are undoubtedly contributing to the aging-related loss of muscle mass and function, since mPTP opening can trigger several atrophy-regulating pathways.”
From Mitochondrial Dynamics and Mitophagy in Skeletal Muscle Health and Aging (2021) · cites this paper as [17]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Akt Promotes Cell Survival by Phosphorylating and Inhibiting a Forkhead Transcription Factor
Brunet, A., Bonni, A., Zigmond, M. J., Lin, M. Z., Juo, P., Hu, L. S., Anderson, M. J., Arden, K. C., Blenis, J., & Greenberg, M. E. (1999) · Cell · doi:10.1016/s0092-8674(00)80595-4 · Cited by 5,594
A System for Stable Expression of Short Interfering RNAs in Mammalian Cells
Brummelkamp, T. R., Bernards, R., & Agami, R. (2002) · Science · doi:10.1126/science.1068999 · Cited by 4,295
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
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
Stitt, T. N., Drujan, D., Clarke, B. A., Panaro, F., Timofeyva, Y., Kline, W. O., Gonzalez, M., Yancopoulos, G. D., & Glass, D. J. (2004) · Molecular Cell · doi:10.1016/s1097-2765(04)00211-4 · Cited by 1,964
Atrogin-1, a muscle-specific F-box protein highly expressed during muscle atrophy
Gomes, M. D., Lecker, S. H., Jagoe, R. T., Navon, A., & Goldberg, A. L. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.251541198 · Cited by 1,774
Self-citationRommel, C., Bodine, S. C., Clarke, B. A., Rossman, R., Nunez, L., Stitt, T. N., Yancopoulos, G. D., & Glass, D. J. (2001) · Nature Cell Biology · doi:10.1038/ncb1101-1009 · Cited by 1,583
Multiple types of skeletal muscle atrophy involve a common program of changes in gene expression
Lecker, S. H., Jagoe, R. T., Gilbert, A., Gomes, M., Baracos, V., Bailey, J., Price, S. R., Mitch, W. E., & Goldberg, A. L. (2004) · The FASEB Journal · doi:10.1096/fj.03-0610com · Cited by 1,539
Self-citationRubinson, D. A., Dillon, C. P., Kwiatkowski, A. V., Sievers, C., Yang, L., Kopinja, J. E., Rooney, D. L., Zhang, M., Ihrig, M. M., McManus, M. T., et al. (2003) · Nature Genetics · doi:10.1038/ng1117 · Cited by 1,499
Insulin-regulated hepatic gluconeogenesis through FOXO1–PGC-1α interaction
Puigserver, P., Rhee, J., Donovan, J., Walkey, C. J., Yoon, J. C., Oriente, F., Kitamura, Y., Altomonte, J., Dong, H., Accili, D., et al. (2003) · Nature · doi:10.1038/nature01667 · Cited by 1,487
Kim, D., Sarbassov, D. D., Ali, S. M., Latek, R. R., Guntur, K., Erdjument‐Bromage, H., Tempst, P., & Sabatini, D. M. (2003) · Molecular Cell · doi:10.1016/s1097-2765(03)00114-x · Cited by 992
NF-κB-Induced Loss of MyoD Messenger RNA: Possible Role in Muscle Decay and Cachexia
D, D. C. G., Mayo, M. W., Madrid, L. V., Wang, C., & Baldwin, A. S. (2000) · Science · doi:10.1126/science.289.5488.2363 · Cited by 922
Peng, X.-D., Xu, P.-Z., Chen, M.-L., Hahn-Windgassen, A., Skeen, J. E., Jacobs, J., Sundararajan, D., Chen, W. S., Crawford, S. E., Coleman, K. G., et al. (2003) · Genes & Development · doi:10.1101/gad.1089403 · Cited by 836
Lecker, S. H., Solomon, V., Mitch, W. E., & Goldberg, A. L. (1999) · Journal of Nutrition · doi:10.1093/jn/129.1.227s · Cited by 742
Self-citationThe Forkhead Transcription Factor Foxo1 Regulates Adipocyte Differentiation
Nakae, J., Kitamura, T., Kitamura, Y., Biggs, W., Arden, K. C., & Accili, D. (2003) · Developmental Cell · doi:10.1016/s1534-5807(02)00401-x · Cited by 729
Furuyama, T., Nakazawa, T., Nakano, I., & Mori, N. (2000) · Biochemical Journal · doi:10.1042/0264-6021:3490629 · Cited by 672
Gilley, J., Coffer, P. J., & Ham, J. (2003) · The Journal of Cell Biology · doi:10.1083/jcb.200303026 · Cited by 659
Musarò, A., McCullagh, K. J. A., Naya, F. J., Olson, E. N., & Rosenthal, N. A. (1999) · Nature · doi:10.1038/23060 · Cited by 652
Nakae, J., Kitamura, T., Silver, D. L., & Accili, D. (2001) · Journal of Clinical Investigation · doi:10.1172/jci12876 · Cited by 652
Nakae, J., Kitamura, T., Silver, D. L., & Accili, D. (2001) · Journal of Clinical Investigation · doi:10.1172/jci200112876 · Cited by 652
Puig, Ó., Marr, M. T., Ruhf, M.-L., & Tjian, R. (2003) · Genes & Development · doi:10.1101/gad.1098703 · Cited by 628
Nakae, J., Biggs, W., Kitamura, T., Cavenee, W. K., Wright, C. V. E., Arden, K. C., & Accili, D. (2002) · Nature Genetics · doi:10.1038/ng890 · Cited by 617
Sacheck, J. M., Ohtsuka, A., McLary, S. C., & Goldberg, A. L. (2004) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00073.2004 · Cited by 606
Self-citationFuruyama, T., Nakazawa, T., Nakano, I., et al. (2000) · Biochemical Journal · doi:10.1042/bj3490629 · Cited by 505
Tran, H. G., Brunet, A., Griffith, E. C., & Greenberg, M. E. (2003) · Science Signaling · doi:10.1126/stke.2003.172.re5 · Cited by 466
A novel mechanism of gene regulation and tumor suppression by the transcription factor FKHR
Ramaswamy, S., Nakamura, N., Sansal, I., Bergeron, L., & Sellers, W. R. (2002) · Cancer Cell · doi:10.1016/s1535-6108(02)00086-7 · Cited by 428
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
Self-citationWhat do we really know about the ubiquitin-proteasome pathway in muscle atrophy?
Jagoe, R. T., & Goldberg, A. L. (2001) · Current Opinion in Clinical Nutrition and Metabolic Care · doi:10.1097/00075197-200105000-00003 · Cited by 399
Self-citationCell-autonomous regulation of cell and organ growth in Drosophila by Akt/PKB
Verdú, J., Buratovich, M., Wilder, E., & Birnbaum, M. (1999) · Nature Cell Biology · doi:10.1038/70293 · Cited by 397
The IKK complex: an integrator of all signals that activate NF-κB?
Israël, A. (2000) · Trends in Cell Biology · doi:10.1016/s0962-8924(00)01729-3 · Cited by 391
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
Self-citationFuruyama, T., Kitayama, K., Yamashita, H., & Mori, N. (2003) · Biochemical Journal · doi:10.1042/bj20030022 · Cited by 330
Glucocorticoids and muscle catabolism
Hasselgren, P.-O. (1999) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/00075197-199905000-00002 · Cited by 297
Skurk, C., Maatz, H., Kim, H.-S., Jiang, Y., Abid, M. R., Aird, W. C., & Walsh, K. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m304736200 · Cited by 271
Self-citationTNF‐α increases ubiquitin‐conjugating activity in skeletal muscle by up‐regulating UbcH2/E2 20k
LI, Y.-P., Lecker, S. H., Chen, Y., Waddell, I. D., Goldberg, A. L., & Reid, M. B. (2003) · The FASEB Journal · doi:10.1096/fj.02-0759com · Cited by 249
Self-citationEvaluation of signals activating ubiquitin-proteasome proteolysis in a model of muscle wasting
Mitch, W. E., Bailey, J. L., Wang, X., Jurkovitz, C. T., Newby, D. E., & Price, S. R. (1999) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1999.276.5.c1132 · Cited by 237
Expressionof Drosophila FOXO regulates growth and can phenocopy starvation
Kramer, J. M., Davidge, J. T., Lockyer, J. M., & Staveley, B. E. (2003) · BMC Developmental Biology · doi:10.1186/1471-213x-3-5 · Cited by 225
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
Self-citationHribal, M. L., Nakae, J., Kitamura, T., Shutter, J. R., & Accili, D. (2003) · The Journal of Cell Biology · doi:10.1083/jcb.200212107 · Cited by 203
FKHR (FOXO1a) is required for myotube fusion of primary mouse myoblasts
Bois, P. R. J., & Grosveld, G. C. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg116 · Cited by 168
Nasrin, N., Ogg, S., Cahill, C. M., Biggs, W., Nui, S., Dore, J., Calvo, D., Shi, Y., Ruvkun, G., & Alexander-Bridges, M. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.190326997 · Cited by 167
Regulation of Angiogenesis by Glycogen Synthase Kinase-3β
Kim, H.-S., Skurk, C., Thomas, S. R., Bialik, A., Suhara, T., Kureishi, Y., Birnbaum, M. J., Keaney, J. F., & Walsh, K. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m206657200 · Cited by 123
Self-citationImae, M., Fu, Z., Yoshida, A., Noguchi, T., & Kato, H. (2003) · Journal of Molecular Endocrinology · doi:10.1677/jme.0.0300253 · Cited by 110
Cited by
Sorted by citations
AKT/PKB Signaling: Navigating the Network
Manning, B. D., & Toker, A. (2017) · Cell · doi:10.1016/j.cell.2017.04.001 · Cited by 3,772
Fiber Types in Mammalian Skeletal Muscles
Schiaffino, S., & Reggiani, C. (2011) · Physiological Reviews · doi:10.1152/physrev.00031.2010 · Cited by 3,022
Self-citationExercise Metabolism and the Molecular Regulation of Skeletal Muscle Adaptation
Egan, B., & Zierath, J. R. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2012.12.012 · Cited by 2,084
Stitt, T. N., Drujan, D., Clarke, B. A., Panaro, F., Timofeyva, Y., Kline, W. O., Gonzalez, M., Yancopoulos, G. D., & Glass, D. J. (2004) · Molecular Cell · doi:10.1016/s1097-2765(04)00211-4 · Cited by 1,964
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
Self-citation
Metadata
- Authors
- Sandri, M., Sandri, C., Gilbert, A., Skurk, C., Calabria, E., Picard, A., Walsh, K., Schiaffino, S., Lecker, S. H., & Goldberg, A. L.
- Affiliations
- Harvard University (US)
- Veneto Institute of Molecular Medicine (IT)
- Beth Israel Deaconess Medical Center (US)
- Boston University (US)
- Corresponding author
- Lecker, Stewart H
- Goldberg, Alfred L
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2004-04
- Volume
- 117
- Issue
- 3
- Pages
- 399-412
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC3619734
- OpenAlex
- W2033797333
- Cited by
- 3,012
- References
- 41
- Citations by year
- 2026: 129 · 2025: 122 · 2024: 121 · 2023: 118 · 2022: 141 · 2021: 153 · 2020: 165 · 2019: 159 · 2018: 151 · 2017: 117 · 2016: 134 · 2015: 171 · 2014: 176 · 2013: 177 · 2012: 150
- FWCI
- 33.75
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Padua Research Archive (University of Padova) (submittedVersion)
- Funders
- National Space Biomedical Research Institute
- European Commission (QLRT-2000-00530)
- National Institutes of Health (DK02707, DK62307)
- Ministero dell’Istruzione, dell’Università e della Ricerca
- Agenzia Spaziale Italiana
- Muscular Dystrophy Association
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › FOXO transcription factor regulation
- Health Sciences › Nursing › Nutrition and Dietetics › Muscle metabolism and nutrition
- Keywords
- FOXO transcription factors, atrogin-1, skeletal muscle atrophy, ubiquitin ligase, PI3K/Akt signaling, insulin-like growth factor I, FOXO3, forkhead transcription factor, starvation, glucocorticoids, myotubes, muscle atrophy, transcriptional regulation
- MeSH terms
- Adenoviridae, Animals, Cells, Cultured, Cloning, Molecular, Fasting, Gene Expression Regulation, Genetic Vectors, Glucocorticoids, Insulin-Like Growth Factor I, Ligases, Models, Biological, Muscle Proteins, Muscular Atrophy, Promoter Regions, Genetic, Proto-Oncogene Proteins, Transcription Factors, Signal Transduction, Protein Serine-Threonine Kinases, Muscle, Skeletal, Phosphatidylinositol 3-Kinases, Muscle Cells, RNA Interference, Ubiquitin-Protein Ligases, SKP Cullin F-Box Protein Ligases, Proto-Oncogene Proteins c-akt, Mice
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
