Role and therapeutic potential of CDK12 in human cancers.
Phosphorylation of the RNA polymerase II C-terminal domain by cyclin-dependent kinases (CDKs) is important for productive transcription. Deregulated transcription-CDKs have been reported in different human cancers. Until recently CDK9 was the only transcription-CDK with a causative role in cancer, but evidence is cumulating of the importance of CDK12. This review summarizes the role of CDK12 in transcription and RNA processing, in maintaining genomic stability/integrity and in tumorigenesis. CDK12 mutations have been reported in many cancers and have been suggested as a cause of defective DNA repair in ovarian carcinoma. CDK12 may have a role as a new therapeutic target in oncology.
Laboratory of Molecular Pharmacology, Oncology Department, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
Rosaria
R
Chilà
Laboratory of Molecular Pharmacology, Oncology Department, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
Federica
F
Guffanti
Laboratory of Molecular Pharmacology, Oncology Department, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy. Electronic address: giovanna.damia@marionegri.it.
Giovanna
G
Damia
D063646:Carcinogenesis / Q000235:genetics*; D018844:Cyclin-Dependent Kinases / Q000235:genetics* / Q000378:metabolism; D056915:DNA Copy Number Variations; D004260:DNA Repair / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D042822:Genomic Instability / Q000235:genetics*; D059765:Homologous Recombination / Q000235:genetics; D006801:Humans; D058990:Molecular Targeted Therapy; D009154:Mutation; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D012319:RNA Polymerase II / Q000378:metabolism*
C447339:CDK12 protein, human; D018844:Cyclin-Dependent Kinases; D012319:RNA Polymerase II
CDK12; DNA repair; Ovarian cancer; Transcription