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A Novel Role of Cdk9/CyclinT2 complexes in skeletal muscle and Rhabdomyosarcoma cells

Marchesi, Irene (2010) A Novel Role of Cdk9/CyclinT2 complexes in skeletal muscle and Rhabdomyosarcoma cells. Doctoral Thesis.

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Abstract

Cyclin dependent kinase 9 (Cdk9) is a member of the cyclin dependent kinase family. The regulatory units of Cdk9 are the T family Cyclins (T1, T2) and Cyclin K1. Cyclin T2 has two forms termed CycT2a and CycT2b that arise by an alternative splicing of the primary transcript. Previous studies underscored a crucial role for Cdk9 in association of Cyclin T2 during skeletal myogenesis. Upon induction of muscle differentiation, MyoD recruits Cdk9/CycT2 on musclespecific gene promoter sequences. This complex is able to phosphorylate the C-terminal domain of RNA polymerase II, enhancing Myod function and promoting myogenic differentiation. Rhabdomyosarcoma (RMS), one of the most common childhood solid tumor, arises from muscle precursor cells and fails to complete both the differentiation program both the irreversibly cell cycle exit, resulting in uncontrolled proliferation and incomplete myogenesis. In RMS, Cdk9 fails to phosphorylate MyoD and the ability of MyoD to arrest cell proliferation and to activate the myogenic program is repressed. The result of this study confirmed the involvement of Cdk9/ CyclinT2 complexes during the myogenesis. Both isoforms of Cyclin T2 are able to activate the myogenic program at different stages of differentiation but CycT2b have a predominant role of in particular during the latest stages. Moreover we demonstred that EZH2 is probably responsible to inhibition of Cdk9 in RMS cells and her overexpression contribuite to inhibition of myogenesis.

Item Type:Doctoral Thesis
ID Code:3871
Publisher:Universita' degli studi di Sassari
Uncontrolled Keywords:Cdk9, CyclinT2, myogenesis, rhabdomyosarcoma
Subjects:Area 05 - Scienze biologiche > BIO/10 Biochimica
Divisions:001 Università di Sassari > 01 Dipartimenti > Scienze fisiologiche, biochimiche e cellulari
Cicli, scuole e corsi:Ciclo 22 > Scuole > Scienze biomolecolari e biotecnologiche > Biochimica, biochimica clinica e biologia molecolare
Deposited On:14 May 2010 13:08

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