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. J. Cell. Biochem. 114: 728–734, 2013. © 2012 Wiley Periodicals, Inc.

[1]  A. Giordano,et al.  The ablation of EZH2 uncovers its crucial role in rhabdomyosarcoma formation , 2012, Cell cycle.

[2]  A. Rice,et al.  Limited redundancy in genes regulated by Cyclin T2 and Cyclin T1 , 2011, BMC Research Notes.

[3]  B. Peterlin,et al.  Cyclin T2 Is Essential for Mouse Embryogenesis , 2009, Molecular and Cellular Biology.

[4]  A. Musarò,et al.  Cdk9‐55: A new player in muscle regeneration , 2008, Journal of cellular physiology.

[5]  B. Peterlin,et al.  Controlling the elongation phase of transcription with P-TEFb. , 2006, Molecular cell.

[6]  A. Giordano,et al.  MyoD recruits the cdk9/cyclin T2 complex on Myogenic‐genes regulatory regions , 2006, Journal of cellular physiology.

[7]  P. Dent,et al.  Characterization of Cdk9(55) and differential regulation of two Cdk9 isoforms. , 2005, Gene.

[8]  C. H. Herrmann,et al.  Differential localization and expression of the Cdk9 42k and 55k isoforms , 2005, Journal of cellular physiology.

[9]  B. Peterlin,et al.  Transcriptional activity and substrate recognition of cyclin T2 from P-TEFb. , 2004, Gene.

[10]  C. Simone,et al.  p38 pathway targets SWI-SNF chromatin-remodeling complex to muscle-specific loci , 2004, Nature Genetics.

[11]  D. Price,et al.  Identification of a novel isoform of Cdk9. , 2003, Gene.

[12]  A. Baldi,et al.  Cyclin T: Three forms for different roles in physiological and pathological functions , 2003, Journal of cellular physiology.

[13]  P. Stiegler,et al.  Activation of MyoD-dependent transcription by cdk9/cyclin T2 , 2002, Oncogene.

[14]  A. Giordano,et al.  Physical interaction between pRb and cdk9/cyclinT2 complex , 2002, Oncogene.

[15]  I. Talianidis,et al.  Coordination of PIC Assembly and Chromatin Remodeling During Differentiation-Induced Gene Activation , 2002, Science.

[16]  M. Rudnicki,et al.  Promoter-specific regulation of MyoD binding and signal transduction cooperate to pattern gene expression. , 2002, Molecular cell.

[17]  P. L. Puri,et al.  Regulation of muscle regulatory factors by DNA‐binding, interacting proteins, and post‐transcriptional modifications , 2000, Journal of cellular physiology.

[18]  P. Stiegler,et al.  Genomic organization, promoter analysis, and chromosomal mapping of the mouse gene encoding Cdk9 , 2000, Journal of cellular biochemistry.

[19]  A. Giordano,et al.  Physical interaction between CDK9 and B-Myb results in suppression of B-Myb gene autoregulation , 2000, Oncogene.

[20]  Junmin Peng,et al.  Cyclin K Functions as a CDK9 Regulatory Subunit and Participates in RNA Polymerase II Transcription* , 1999, The Journal of Biological Chemistry.

[21]  A. Giordano,et al.  CDK9 (PITALRE): A multifunctional cdc2‐related kinase , 1998, Journal of cellular physiology.

[22]  A. Giordano,et al.  Cloning of murine CDK9/PITALRE and its tissue‐specific expression in development , 1998, Journal of cellular physiology.

[23]  H. Arnold,et al.  Muscle differentiation: more complexity to the network of myogenic regulators. , 1998, Current opinion in genetics & development.

[24]  J. Milton,et al.  Identification of multiple cyclin subunits of human P-TEFb. , 1998, Genes & development.

[25]  Brian D. Dynlacht,et al.  Regulation of transcription by proteins that control the cell cycle , 1997, Nature.

[26]  A. Giordano,et al.  CDC2‐related kinase PITALRE phosphorylates pRb exclusively on serine and is widely expressed in human tissues , 1997, Journal of cellular physiology.

[27]  C. Sherr.  Cancer Cell Cycles , 1996, Science.

[28]  B. Wold,et al.  Skeletal muscle determination and differentiation: story of a core regulatory network and its context. , 1996, Current opinion in cell biology.

[29]  D. Price,et al.  Control of RNA Polymerase II Elongation Potential by a Novel Carboxyl-terminal Domain Kinase* , 1996, The Journal of Biological Chemistry.

[30]  E. Olson,et al.  Combinatorial control of muscle development by basic helix-loop-helix and MADS-box transcription factors. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[31]  A. Lassar,et al.  Wiring diagrams: regulatory circuits and the control of skeletal myogenesis. , 1994, Current opinion in cell biology.

[32]  A. Giordano,et al.  PITALRE, a nuclear CDC2-related protein kinase that phosphorylates the retinoblastoma protein in vitro. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[33]  E. Olson,et al.  Interplay between proliferation and differentiation within the myogenic lineage. , 1992, Developmental biology.

[34]  H. Weintraub,et al.  Acquisition of myogenic specificity by replacement of three amino acid residues from MyoD into E12. , 1992, Science.

[35]  D. Lockshon,et al.  MyoD is a sequence-specific DNA binding protein requiring a region of myc homology to bind to the muscle creatine kinase enhancer , 1989, Cell.

[36]  A. Giordano,et al.  Abrogation of signal-dependent activation of the cdk9/cyclin T2a complex in human RD rhabdomyosarcoma cells , 2007, Cell Death and Differentiation.