Expanding role of cyclin dependent kinases in cytokine inducible gene expression

Allan R. Brasier

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

The Positive Transcriptional Elongation Factor b (P-TEFb), a heterodimer of CDK9 and Cyclin T1, is widely implicated in control of basal gene expression. Here, P-TEFb is involved in transitioning paused RNA polymerase II to enter productive transcriptional elongation mode by phosphorylating negative elongation factors and Ser2 of the heptad repeat in the RNA Pol II COOH terminal domain (CTD). This perspective will examine recent work in two unrelated inducible signaling pathways that illustrate the central role of P-TEFb in mediating cytokine inducible transcription networks. Specifically, P-TEFb has been recently discovered to play a key role in TNF-inducible NFκB activation and IL-6-inducible STAT3 signaling. In these signaling cascades, P-TEFb forms protein complexes with the activated nuclear RelA and STAT3 transcription factor in the cellular nucleoplasm, an association important for P-TEFb's promoter targeting. Studies using siRNA-mediated knockdown and/or selective CDK inhibitors show that P-TEFb plays a functional role in activation of a subset of NFκB-dependent targets and all STAT3-dependent genes studied to date. Interestingly, cytokine inducible genes that are sensitive to P-TEFb inhibition share an induction mechanism requiring inducible RNA Pol II recruitment. Chromatin immunoprecipitation studies have preliminarily indicated that this recruitment is dependent on CDK enzymatic activity. The potential of inhibiting P-TEFb as an anti-inflammatory therapy in innate immunity and systemic inflammation will be discussed.

Original languageEnglish (US)
Pages (from-to)2661-2666
Number of pages6
JournalCell Cycle
Volume7
Issue number17
StatePublished - Sep 1 2008

Fingerprint

Transcriptional Elongation Factors
Cyclin-Dependent Kinases
Gene expression
Cytokines
Gene Expression
RNA Polymerase II
Positive Transcriptional Elongation Factor B
Cyclin T
Genes
Chemical activation
STAT3 Transcription Factor
Chromatin Immunoprecipitation
Transcription
Innate Immunity
Small Interfering RNA
Chromatin
Elongation
Interleukin-6
Anti-Inflammatory Agents

Keywords

  • Cyclin dependent kinases (CDK)
  • Inflammation
  • NFκB
  • PTEF-b
  • STAT3

ASJC Scopus subject areas

  • Cell Biology
  • Biochemistry
  • Molecular Biology

Cite this

Expanding role of cyclin dependent kinases in cytokine inducible gene expression. / Brasier, Allan R.

In: Cell Cycle, Vol. 7, No. 17, 01.09.2008, p. 2661-2666.

Research output: Contribution to journalArticle

Brasier, Allan R. / Expanding role of cyclin dependent kinases in cytokine inducible gene expression. In: Cell Cycle. 2008 ; Vol. 7, No. 17. pp. 2661-2666.
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