Identification of Ubiquitin Ligases Required for Skeletal Muscle Atrophy-Reference-Cited by-同舟云学术

Identification of Ubiquitin Ligases Required for Skeletal Muscle Atrophy

Published:2001-11-23 Issue:5547 Volume:294 Page:1704-1708
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Bodine Sue C.¹,Latres Esther¹,Baumhueter Susanne²,Lai Venus K.-M.¹,Nunez Lorna¹,Clarke Brian A.¹,Poueymirou William T.¹,Panaro Frank J.¹,Na Erqian¹,Dharmarajan Kumar¹,Pan Zhen-Qiang³,Valenzuela David M.¹,DeChiara Thomas M.¹,Stitt Trevor N.¹,Yancopoulos George D.¹,Glass David J.¹

Affiliation:

1. Regeneron Pharmaceuticals, 777 Old Saw Mill River Road, Tarrytown, NY, 10591–6707, USA.

2. Applied Biosystems, 850 Lincoln Center Drive, Foster City, CA 94404, USA.

3. Derald H. Ruttenberg Cancer Center, Mount Sinai School of Medicine, New York, NY, 10029–6574, USA.

Abstract

Skeletal muscle adapts to decreases in activity and load by undergoing atrophy. To identify candidate molecular mediators of muscle atrophy, we performed transcript profiling. Although many genes were up-regulated in a single rat model of atrophy, only a small subset was universal in all atrophy models. Two of these genes encode ubiquitin ligases: Muscle RING Finger 1 ( MuRF1 ), and a gene we designate Muscle Atrophy F-box ( MAFbx ), the latter being a member of the SCF family of E3 ubiquitin ligases. Overexpression of MAFbx in myotubes produced atrophy, whereas mice deficient in either MAFbx or MuRF1 were found to be resistant to atrophy. These proteins are potential drug targets for the treatment of muscle atrophy.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Reference20 articles.

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3. S. C. Bodine et al. Nature Cell Biol. 3 1013 (2001).

4. Additional data and methods used in this study are described in the supplementary Web material available on Science Online at www.sciencemag.org/cgi/content/full/1065874/DC1. GenBank accession numbers are as follows: rat MAFbx ; human MAFbx ; and rat MuRF1 . For Northern methods and probe details ref. (2) of Web material. Knockouts were done with the proprietary Velocigene technology which allows for the rapid and high-throughput generation of custom gene mutations in mice (T. M. De Chiara W. T. Poueymirou D. M. Valenzuela G. D. Yancopoulos unpublished data).

5. REGULATION OF SKELETAL MUSCLE PROTEIN TURNOVER DURING SEPSIS

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