Activation and function of murine Cyclin T2A and Cyclin T2B during skeletal muscle differentiation.
Cyclin-dependent kinase 9 (Cdk9) is a serine-threonine kinase, involved in many cellular processes. The regulatory units of Cdk9 are the T family Cyclins (T1, T2) and Cyclin K. Cyclin T2 has two forms termed Cyclin T2a and Cyclin T2b that arise by an alternative splicing of the primary transcript. Upon induction of muscle differentiation, MyoD recruits Cdk9/Cyclin T2 on muscle-specific gene promoter sequences. This complex is able to phosphorylate the C-terminal domain of RNA polymerase II, enhancing MyoD function and promoting myogenic differentiation. This work focuses on the characterization of two murine Cyclin T2 isoforms and the evaluation of the role of Cdk9/Cyclin T2 complexes during the skeletal muscle differentiation. This study demonstrated a predominant expression of isoform b in all stages of differentiation. Moreover, both isoforms of Cyclin T2 are able to activate the myogenic program but Cyclin T2b has a predominant role, in particular during the latest stages.
Department of Biomedical Sciences, Division of Biochemistry and National Institute of Biostructures and Biosystems, University of Sassari, Sassari, Italy.
Irene
I
Marchesi
Valentina
V
Nieddu
Valentina
V
Caracciolo
Margherita
M
Maioli
Leonardo
L
Gaspa
Antonio
A
Giordano
Luigi
L
Bagella
D017398:Alternative Splicing; D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation / Q000235:genetics*; D002455:Cell Division; D002478:Cells, Cultured; D056906:Cyclin T / Q000235:genetics* / Q000378:metabolism*; D042863:Cyclin-Dependent Kinase 9 / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D018482:Muscle, Skeletal / Q000166:cytology* / Q000196:embryology / Q000378:metabolism*; D017570:MyoD Protein / Q000378:metabolism; D032446:Myoblasts; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D020033:Protein Isoforms / Q000235:genetics; D012319:RNA Polymerase II / Q000378:metabolism; D017422:Sequence Analysis, DNA; D014158:Transcription, Genetic
D056906:Cyclin T; D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; D020033:Protein Isoforms; C467972:Cdk9 protein, mouse; D042863:Cyclin-Dependent Kinase 9; D012319:RNA Polymerase II