The 31-kDa caspase-generated cleavage product of p130Cas antagonizes the action of MyoD during myogenesis

Da Eun Jeong; Eun Kyung Lee; Woo Keun Song; Wook Kim

doi:10.1016/j.bbrc.2014.01.085

The 31-kDa caspase-generated cleavage product of p130Cas antagonizes the action of MyoD during myogenesis

Da Eun Jeong, Eun Kyung Lee, Woo Keun Song, Wook Kim

Department of Biochemistry

Research output: Contribution to journal › Article › peer-review

4 Scopus citations

Abstract

Myogenesis is regulated by the basic helix-loop-helix (bHLH) myogenic regulatory factor MyoD, which induces muscle-specific gene expression by binding to the E-box sequence as a heterodimer with ubiquitous bHLH E2A (E12/E47) proteins. Here, we report that a 31-kDa caspase-generated cleavage product of Crk-associated substrate (p130Cas), herein called 31-kDa, is downregulated during muscle cell differentiation. 31-kDa contains a helix-loop-helix (HLH) domain that shows greater sequence homology with Id (inhibitor of DNA binding) proteins than with bHLH proteins. This HLH domain, lacking the basic region required for DNA binding, mediated the direct interaction of 31-kDa with MyoD. Overexpression of 31-kDa in C3H10T1/2 cells inhibited not only the transcriptional activation of p21^Waf1/Cip1 and E-box-dependent muscle-specific genes by MyoD and/or E2A but also MyoD-induced myosin heavy chain expression and myogenic conversion. In sum, our results suggest a role for 31-kDa as a negative regulator of MyoD in the muscle differentiation program.

Original language	English
Pages (from-to)	509-513
Number of pages	5
Journal	Biochemical and Biophysical Research Communications
Volume	444
Issue number	4
DOIs	https://doi.org/10.1016/j.bbrc.2014.01.085
State	Published - 21 Feb 2014

Bibliographical note

Funding Information:
This work was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) , funded by the Korean Ministry of Education (No. 2009-0093826 ). W.K.S. was supported by the Bio Imaging and Cell Dynamics Research Center, funded by the Korean Ministry of Science , ICT and Future Planning (MSIP) ( 2007-0056157 ). E.K.L. was supported by the National Research Foundation of Korea (NRF), funded by the Korean MSIP ( 2012M3A9D1054476 ).

Keywords

31-kDa fragment
MyoD
Myogenesis
bHLH
p130Cas

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10.1016/j.bbrc.2014.01.085

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title = "The 31-kDa caspase-generated cleavage product of p130Cas antagonizes the action of MyoD during myogenesis",

abstract = "Myogenesis is regulated by the basic helix-loop-helix (bHLH) myogenic regulatory factor MyoD, which induces muscle-specific gene expression by binding to the E-box sequence as a heterodimer with ubiquitous bHLH E2A (E12/E47) proteins. Here, we report that a 31-kDa caspase-generated cleavage product of Crk-associated substrate (p130Cas), herein called 31-kDa, is downregulated during muscle cell differentiation. 31-kDa contains a helix-loop-helix (HLH) domain that shows greater sequence homology with Id (inhibitor of DNA binding) proteins than with bHLH proteins. This HLH domain, lacking the basic region required for DNA binding, mediated the direct interaction of 31-kDa with MyoD. Overexpression of 31-kDa in C3H10T1/2 cells inhibited not only the transcriptional activation of p21Waf1/Cip1 and E-box-dependent muscle-specific genes by MyoD and/or E2A but also MyoD-induced myosin heavy chain expression and myogenic conversion. In sum, our results suggest a role for 31-kDa as a negative regulator of MyoD in the muscle differentiation program.",

keywords = "31-kDa fragment, MyoD, Myogenesis, bHLH, p130Cas",

author = "Jeong, {Da Eun} and Lee, {Eun Kyung} and Song, {Woo Keun} and Wook Kim",

note = "Funding Information: This work was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) , funded by the Korean Ministry of Education (No. 2009-0093826 ). W.K.S. was supported by the Bio Imaging and Cell Dynamics Research Center, funded by the Korean Ministry of Science , ICT and Future Planning (MSIP) ( 2007-0056157 ). E.K.L. was supported by the National Research Foundation of Korea (NRF), funded by the Korean MSIP ( 2012M3A9D1054476 ).",

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AU - Jeong, Da Eun

AU - Lee, Eun Kyung

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AU - Kim, Wook

N1 - Funding Information: This work was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) , funded by the Korean Ministry of Education (No. 2009-0093826 ). W.K.S. was supported by the Bio Imaging and Cell Dynamics Research Center, funded by the Korean Ministry of Science , ICT and Future Planning (MSIP) ( 2007-0056157 ). E.K.L. was supported by the National Research Foundation of Korea (NRF), funded by the Korean MSIP ( 2012M3A9D1054476 ).

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Y1 - 2014/2/21

N2 - Myogenesis is regulated by the basic helix-loop-helix (bHLH) myogenic regulatory factor MyoD, which induces muscle-specific gene expression by binding to the E-box sequence as a heterodimer with ubiquitous bHLH E2A (E12/E47) proteins. Here, we report that a 31-kDa caspase-generated cleavage product of Crk-associated substrate (p130Cas), herein called 31-kDa, is downregulated during muscle cell differentiation. 31-kDa contains a helix-loop-helix (HLH) domain that shows greater sequence homology with Id (inhibitor of DNA binding) proteins than with bHLH proteins. This HLH domain, lacking the basic region required for DNA binding, mediated the direct interaction of 31-kDa with MyoD. Overexpression of 31-kDa in C3H10T1/2 cells inhibited not only the transcriptional activation of p21Waf1/Cip1 and E-box-dependent muscle-specific genes by MyoD and/or E2A but also MyoD-induced myosin heavy chain expression and myogenic conversion. In sum, our results suggest a role for 31-kDa as a negative regulator of MyoD in the muscle differentiation program.

AB - Myogenesis is regulated by the basic helix-loop-helix (bHLH) myogenic regulatory factor MyoD, which induces muscle-specific gene expression by binding to the E-box sequence as a heterodimer with ubiquitous bHLH E2A (E12/E47) proteins. Here, we report that a 31-kDa caspase-generated cleavage product of Crk-associated substrate (p130Cas), herein called 31-kDa, is downregulated during muscle cell differentiation. 31-kDa contains a helix-loop-helix (HLH) domain that shows greater sequence homology with Id (inhibitor of DNA binding) proteins than with bHLH proteins. This HLH domain, lacking the basic region required for DNA binding, mediated the direct interaction of 31-kDa with MyoD. Overexpression of 31-kDa in C3H10T1/2 cells inhibited not only the transcriptional activation of p21Waf1/Cip1 and E-box-dependent muscle-specific genes by MyoD and/or E2A but also MyoD-induced myosin heavy chain expression and myogenic conversion. In sum, our results suggest a role for 31-kDa as a negative regulator of MyoD in the muscle differentiation program.

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The 31-kDa caspase-generated cleavage product of p130Cas antagonizes the action of MyoD during myogenesis

Abstract

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Keywords

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