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Journal ArticleDOI

Identification of Ubiquitin Ligases Required for Skeletal Muscle Atrophy

Sue C. Bodine, +15 more
- 23 Nov 2001 - 
- Vol. 294, Iss: 5547, pp 1704-1708
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TLDR
Two genes encode ubiquitin ligases that are potential drug targets for the treatment of muscle atrophy, and mice deficient in either MAFbx orMuRF1 were found to be resistant to atrophy.
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.

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Journal ArticleDOI

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

Daniel J. Klionsky, +2522 more
- 21 Jan 2016 - 
TL;DR: In this paper, the authors present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macro-autophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes.
Journal ArticleDOI

The Ubiquitin-Proteasome Proteolytic Pathway: Destruction for the Sake of Construction

Michael H. Glickman, +1 more
- 01 Apr 2002 - 
TL;DR: It is clear now that degradation of cellular proteins is a highly complex, temporally controlled, and tightly regulated process that plays major roles in a variety of basic pathways during cell life and death as well as in health and disease.
Journal ArticleDOI

The Calpain System

Darrell E Goll, +4 more
- 01 Jul 2003 - 
TL;DR: How calpain activity is regulated in cells is still unclear, but the calpains ostensibly participate in a variety of cellular processes including remodeling of cytoskeletal/membrane attachments, different signal transduction pathways, and apoptosis.
Journal ArticleDOI

Foxo Transcription Factors Induce the Atrophy-Related Ubiquitin Ligase Atrogin-1 and Cause Skeletal Muscle Atrophy

Marco Sandri, +9 more
- 30 Apr 2004 - 
TL;DR: It is shown 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.
Journal ArticleDOI

The IGF-1/PI3K/Akt Pathway Prevents Expression of Muscle Atrophy-Induced Ubiquitin Ligases by Inhibiting FOXO Transcription Factors

Trevor Stitt, +8 more
- 07 May 2004 - 
TL;DR: Akt is not only capable of activating prosynthetic pathways, as previously demonstrated, but is simultaneously and dominantly able to suppress catabolic pathways, allowing it to prevent glucocorticoid and denervation-induced muscle atrophy.
References
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Journal ArticleDOI

Akt/mTOR pathway is a crucial regulator of skeletal muscle hypertrophy and can prevent muscle atrophy in vivo.

Sue C. Bodine, +10 more
- 01 Nov 2001 - 
TL;DR: It is concluded that the activation of the Akt/mTOR pathway and its downstream targets, p70S6K and PHAS-1/4E-BP1, is requisitely involved in regulating skeletal muscle fibre size, and that activation of this pathway can oppose muscle atrophy induced by disuse.
Journal ArticleDOI

Mediation of IGF-1-induced skeletal myotube hypertrophy by PI(3)K/Akt/mTOR and PI(3)K/Akt/GSK3 pathways

Christian Rommel, +7 more
- 01 Nov 2001 - 
TL;DR: It is shown that Akt promotes hypertrophy by activating downstream signalling pathways previously implicated in activating protein synthesis: the pathways downstream of mammalian target of rapamycin (mTOR) and the pathway activated by phosphorylating and thereby inhibiting glycogen synthase kinase 3 (GSK3).
Journal ArticleDOI

F-Box Proteins Are Receptors that Recruit Phosphorylated Substrates to the SCF Ubiquitin-Ligase Complex

Dorota Skowyra, +4 more
- 17 Oct 1997 - 
TL;DR: The ubiquitination pathway for the Cdk inhibitor Sic1 is reconstituted using recombinant proteins and the constituents of the SCF complex are members of protein families, likely to serve as the prototype for a large class of E3s formed by combinatorial interactions of related family members.
Journal ArticleDOI

RING finger proteins: mediators of ubiquitin ligase activity.

Claudio A. P. Joazeiro, +1 more
- 01 Sep 2000 - 
TL;DR: The field of intracellular protein degradation now leaves the era where mediators of substrate-specific ubiquitination were scarce and enters a new and exciting phase where databases provide us with a large number of candidate E3s awaiting characterization.
Journal ArticleDOI

The F-box protein family.

Edward T. Kipreos, +1 more
- 10 Nov 2000 - 
TL;DR: The F-box is a protein motif of approximately 50 amino acids that functions as a site of protein-protein interaction that links the F- box protein to other components of the SCF complex by binding the core SCF component Skp I.
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Atrogin-1, a muscle-specific F-box protein highly expressed during muscle atrophy

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Foxo Transcription Factors Induce the Atrophy-Related Ubiquitin Ligase Atrogin-1 and Cause Skeletal Muscle Atrophy

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Multiple types of skeletal muscle atrophy involve a common program of changes in gene expression

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The IGF-1/PI3K/Akt Pathway Prevents Expression of Muscle Atrophy-Induced Ubiquitin Ligases by Inhibiting FOXO Transcription Factors

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