Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/98278
Title: Identification of atrogin-1-targeted proteins during the myostatin-induced skeletal muscle wasting
Authors: Lokireddy, Sudarsanareddy
Wijesoma, Isuru Wijerupage
Sze, Siu Kwan
McFarlane, Craig
Kambadur, Ravi
Sharma, Mridula
Keywords: DRNTU::Science::Biological sciences
Issue Date: 2012
Source: Lokireddy, S., Wijesoma, I. W., Sze, S. K., McFarlane, C., Kambadur, R., & Sharma, M. (2012). Identification of atrogin-1-targeted proteins during the myostatin-induced skeletal muscle wasting. American Journal of Physiology: Cell Physiology, 303(5), C512-C529.
Series/Report no.: American journal of physiology : cell physiology
Abstract: Atrogin-1, a muscle-specific E3 ligase, targets MyoD for degradation through the ubiquitin-proteasome-mediated system. Myostatin, a member of the transforming growth factor-β superfamily, potently inhibits myogenesis by lowering MyoD levels. While atrogin-1 is upregulated by myostatin, it is currently unknown whether atrogin-1 plays a role in mediating myostatin signaling to regulate myogenesis. In this report, we have confirmed that atrogin-1 increasingly interacts with MyoD upon recombinant human myostatin (hMstn) treatment. The absence of atrogin-1, however, led to elevated MyoD levels and permitted the differentiation of atrogin-1−/− primary myoblast cultures despite the presence of exogenous myostatin. Furthermore, inactivation of atrogin-1 rescued myoblasts from growth inhibition by hMstn. Therefore, these results highlight the central role of atrogin-1 in regulating myostatin signaling during myogenesis. Currently, there are only two known targets of atrogin-1. Thus, we next characterized the associated proteins of atrogin-1 in control and hMstn-treated C2C12 cell cultures by stably expressing tagged atrogin-1 in myoblasts and myotubes, and sequencing the coimmunoprecipitated proteome. We found that atrogin-1 putatively interacts with sarcomeric proteins, transcriptional factors, metabolic enzymes, components of translation, and spliceosome formation. In addition, we also identified that desmin and vimentin, two components of the intermediate filament in muscle, directly interacted with and were degraded by atrogin-1 in response to hMstn. In summary, the muscle wasting effects of the myostatin-atrogin-1 axis are not only limited to the degradation of MyoD and eukaryotic translation initiation factor 3 subunit f, but also encompass several proteins that are involved in a wide variety of cellular activities in the muscle.
URI: https://hdl.handle.net/10356/98278
http://hdl.handle.net/10220/12435
DOI: http://dx.doi.org/10.1152/ajpcell.00402.2011
Rights: © 2012 The American Physiological Society.
Fulltext Permission: none
Fulltext Availability: No Fulltext
Appears in Collections:SBS Journal Articles

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