The Ubiquitin Proteasome System and Muscle Development

Kim, Johnny; Hoppe, Thorsten

doi:10.1002/9783527620227.ch2

Cited by 1 publication

(2 citation statements)

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“…Degradation of muscle proteins occurs through several mechanisms but more importantly by the UPS. The fast and time-specific regulation of protein levels by the UPS, is crucial for muscle development [8]. Several key factors in myogenesis are known to be regulated by the UPS, namely myogenic factors, such as MyoD and Myogenin, and membrane proteins, like β-catenin and integrins [8], [10], [13], [14], [15].…”

Section: Discussionmentioning

confidence: 99%

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Ataxin-3 Plays a Role in Mouse Myogenic Differentiation through Regulation of Integrin Subunit Levels

et al. 2010

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BackgroundDuring myogenesis several transcription factors and regulators of protein synthesis and assembly are rapidly degraded by the ubiquitin-proteasome system (UPS). Given the potential role of the deubiquitinating enzyme (DUB) ataxin-3 in the UPS, and the high expression of the murine ataxin-3 homolog in muscle during embryogenesis, we sought to define its role in muscle differentiation.Methodology/Principal FindingsUsing immunofluorescence analysis, we found murine ataxin-3 (mATX3) to be highly expressed in the differentiated myotome of E9.5 mouse embryos. C2C12 myoblasts depleted of mATX3 by RNA interference exhibited a round morphology, cell misalignment, and a delay in differentiation following myogenesis induction. Interestingly, these cells showed a down-regulation of α5 and α7 integrin subunit levels both by immunoblotting and immunofluorescence. Mouse ATX3 was found to interact with α5 integrin subunit and to stabilize this protein by repressing its degradation through the UPS. Proteomic analysis of mATX3-depleted C2C12 cells revealed alteration of the levels of several proteins related to integrin signaling.ConclusionsAtaxin-3 is important for myogenesis through regulation of integrin subunit levels.

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Section: Discussionmentioning

confidence: 99%

“…Many transcription factors and other proteins participating in the aforementioned processes are rapidly degraded by the UPS, including MyoD [8], Myf5 [9], myogenin [10], Pax3 [11], Id proteins [12], β-catenin [13], [14], and α5 integrin subunit [15].…”

Section: Introductionmentioning

confidence: 99%