Dissecting the Pol II transcription cycle and derailing cancer with CDK inhibitors

Pabitra K. Parua, Robert P. Fisher

Research output: Contribution to journalReview articlepeer-review

19 Scopus citations

Abstract

Largely non-overlapping sets of cyclin-dependent kinases (CDKs) regulate cell division and RNA polymerase II (Pol II)-dependent transcription. Here we review the molecular mechanisms by which specific CDKs are thought to act at discrete steps in the transcription cycle and describe the recent emergence of transcriptional CDKs as promising drug targets in cancer. We emphasize recent advances in understanding the transcriptional CDK network that were facilitated by development and deployment of small-molecule inhibitors with increased selectivity for individual CDKs. Unexpectedly, several of these compounds have also shown selectivity in killing cancer cells, despite the seemingly universal involvement of their target CDKs during transcription in all cells. Finally, we describe remaining and emerging challenges in defining functions of individual CDKs in transcription and co-transcriptional processes and in leveraging CDK inhibition for therapeutic purposes. [Figure not available: see fulltext.].

Original languageEnglish (US)
Pages (from-to)716-724
Number of pages9
JournalNature Chemical Biology
Volume16
Issue number7
DOIs
StatePublished - Jul 1 2020
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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