title: 55K isoform of CDK9 associates with Ku70 and is involved in DNA repair.
abstract: Positive elongation factor b (P-TEFb) is a cellular protein kinase that is required for RNA polymerase II (RNAP II) transcriptional elongation of protein coding genes. P-TEFb is a set of different molecular complexes, each containing CDK9 as the catalytic subunit. There are two isoforms of the CDK9 protein - the major 42KDa CDK9 isoform and the minor 55KDa isoform that is translated from an in-frame mRNA that arises from an upstream transcriptional start site. We found that shRNA depletion of the 55K CDK9 protein in HeLa cells induces apoptosis and double-strand DNA breaks (DSBs). The levels of apoptosis and DSBs induced by the depletion were reduced by expression of a 55K CDK9 protein variant resistant to the shRNA, indicating that these phenotypes are the consequence of depletion of the 55K protein and not off-target effects. We also found that the 55K CDK9 protein, but not the 42K CDK9 protein, specifically associates with Ku70, a protein involved in DSB repair. Our findings suggest that the 55K CDK9 protein may function in repair of DNA through an association with Ku70.
authors.affiliation: Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Hongbing
authors.initials: H
authors.lastname: Liu
authors.forename: Christine H
authors.initials: CH
authors.lastname: Herrmann
authors.forename: Karen
authors.initials: K
authors.lastname: Chiang
authors.forename: Tzu-Ling
authors.initials: TL
authors.lastname: Sung
authors.forename: Sung-Hwan
authors.initials: SH
authors.lastname: Moon
authors.forename: Lawrence A
authors.initials: LA
authors.lastname: Donehower
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Rice
mesh_terms: D034961:Antigens, Nuclear / Q000378:metabolism*; D002460:Cell Line; D042863:Cyclin-Dependent Kinase 9 / Q000235:genetics / Q000378:metabolism*; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005822:Genetic Vectors; D006367:HeLa Cells; D006801:Humans; D000072200:Ku Autoantigen; D035683:MicroRNAs / Q000235:genetics; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism
chemical_list: D034961:Antigens, Nuclear; D004268:DNA-Binding Proteins; D035683:MicroRNAs; D020033:Protein Isoforms; D042863:Cyclin-Dependent Kinase 9; C000606509:Xrcc6 protein, human; D000072200:Ku Autoantigen