Is TFIIH the new Achilles heel of cancer cells?

Transcription. 2018;9(1):47-51. doi: 10.1080/21541264.2017.1331723. Epub 2017 Oct 4.

Abstract

TFIIH is a 10-subunit complex involved in transcription and DNA repair. It contains several enzymatic activities including a ATP-dependent DNA translocase in XPB and a cyclin-dependent kinase in CDK7. Recently the discovery of several XPB and CDK7 inhibitors with specific impact on the transcriptional addiction of many tumors pinpointed these activities as potential target in cancer chemotherapy. Unexpectedly a basal transcription factor involved in global mRNA expression now emerges a one of the most clinically promising Achilles heels of cancerous cells. These inhibitors also proved to be useful tools to unveil new functions of TFIIH in gene expression.

Keywords: DNA repair; TFIIH; genomic instability; helicase.

Publication types

  • Review

MeSH terms

  • Cyclin-Dependent Kinase-Activating Kinase
  • Cyclin-Dependent Kinases / antagonists & inhibitors
  • DNA Helicases / antagonists & inhibitors
  • DNA Repair / drug effects*
  • DNA-Binding Proteins / antagonists & inhibitors
  • Humans
  • Neoplasms / drug therapy*
  • Neoplasms / enzymology
  • Neoplasms / genetics
  • Neoplasms / pathology
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Transcription Factor TFIIH / antagonists & inhibitors*
  • Transcription Factor TFIIH / metabolism*
  • Transcription, Genetic / drug effects*

Substances

  • DNA-Binding Proteins
  • RNA, Messenger
  • XPBC-ERCC-3 protein
  • Transcription Factor TFIIH
  • Cyclin-Dependent Kinases
  • DNA Helicases
  • Cyclin-Dependent Kinase-Activating Kinase
  • CDK7 protein, human