Cdk9-55: a new player in muscle regeneration.
Adult skeletal muscle contains a specialized population of myogenic quiescent stem cells, termed satellite cells, which contribute to repair myofibers after injury. During muscle regeneration, satellite cells exit their normal quiescent state, proliferate, activating MyoD and Myf-5 expression, and finally differentiate and fuse to reconstitute the injured muscle architecture. We have previously reported that cdk9 is required for myogenesis in vitro by activating MyoD-dependent transcription. In myoblasts induced to differentiate, MyoD recruits cdk9 on the chromatin of muscle-specific regulatory regions. This event correlates with chromatin-modifying enzyme recruitment and phosphorylation of cdk9-specific target residues at the carboxyl-terminal domain of RNA polymerase II. Here we report that a second cdk9 isoform, termed cdk9-55, plays a fundamental role in muscle regeneration and differentiation in vivo. This alternative form is specifically induced in injured myofibers and its activity is strictly required for the completion of muscle regeneration process.
Giacinti
Cristina
C
Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, USA.
Musarò
Antonio
A
De Falco
Giulia
G
Jourdan
Isabelle
I
Molinaro
Mario
M
Bagella
Luigi
L
Simone
Cristiano
C
Giordano
Antonio
A
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D042863:Cyclin-Dependent Kinase 9 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D024510:Muscle Development / Q000502:physiology*; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000166:cytology / Q000502:physiology; D017570:MyoD Protein / Q000235:genetics / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D012038:Regeneration / Q000502:physiology*; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*
D017570:MyoD Protein; D020033:Protein Isoforms; D042863:Cyclin-Dependent Kinase 9