The 31-kDa caspase-generated cleavage product of p130Cas antagonizes the action of MyoD during myogenesis.
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.
Department of Molecular Science and Technology, Ajou University, Suwon 443-749, South Korea.
Da Eun
DE
Jeong
Department of Biochemistry, College of Medicine, The Catholic University of Korea, Seoul 137-701, South Korea.
Eun Kyung
EK
Lee
Department of Life Science, Bio Imaging and Cell Dynamics Research Center, Gwangju Institute of Science and Technology, Gwangju 500-712, South Korea. Electronic address: wksong@gist.ac.kr.
Woo Keun
WK
Song
Department of Molecular Science and Technology, Ajou University, Suwon 443-749, South Korea. Electronic address: wookkim21@ajou.ac.kr.
Wook
W
Kim
D000818:Animals; D020169:Caspases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D050719:Crk-Associated Substrate Protein / Q000378:metabolism*; D015536:Down-Regulation; D018507:Gene Expression Regulation, Developmental; D018257:Helix-Loop-Helix Motifs; D051379:Mice; D024510:Muscle Development; D017570:MyoD Protein / Q000378:metabolism*
D050719:Crk-Associated Substrate Protein; D017570:MyoD Protein; D020169:Caspases
31-kDa fragment; MyoD; Myogenesis; bHLH; p130Cas