Role and therapeutic potential of CDK12 in human cancers

Cancer Treat Rev. 2016 Nov:50:83-88. doi: 10.1016/j.ctrv.2016.09.003. Epub 2016 Sep 14.

Abstract

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.

Keywords: CDK12; DNA repair; Ovarian cancer; Transcription.

Publication types

  • Review

MeSH terms

  • Carcinogenesis / genetics*
  • Cyclin-Dependent Kinases / genetics*
  • Cyclin-Dependent Kinases / metabolism
  • DNA Copy Number Variations
  • DNA Repair / genetics
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Genomic Instability / genetics*
  • Homologous Recombination / genetics
  • Humans
  • Molecular Targeted Therapy
  • Mutation
  • Neoplasms / drug therapy
  • Neoplasms / genetics*
  • Neoplasms / metabolism
  • Ovarian Neoplasms / drug therapy
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / metabolism
  • Phosphorylation
  • RNA Polymerase II / metabolism*

Substances

  • CDK12 protein, human
  • Cyclin-Dependent Kinases
  • RNA Polymerase II