P-TEFb is a crucial co-factor for Myc transactivation

Barbara Gargano, Stefano Amente, Barbara Majello, Luigi Lania

Research output: Contribution to journalArticle

Abstract

Myc forms an heterodimer with Max and operates as a transcription factor upon binding to specific DNA sites in cellular chromatin. In addition to recruit histone acetylation activity, Myc binds to the positive transcription elongation factor b (P-TEFb) which consists of the cyclin-dependent kinase CKD9 and its regulatory subunit cyclin T. P-TEFb phosphorylates the carboxyl-terminal-domain (CTD) of the larger subunit of RNA polymerase II as well as negative elongation factors allowing efficient transcription elongation. Here, we report that Myc binds, as heterodimer with Max, exclusively the core active P-TEFb complex, and it recruits P-TEFb at Myc targets in vivo. Pharmacological inhibition of P-TEFb by 5.6-di-chloro-1-b-D-ribofuranosyl- bensimidazole (DRB) specifically inhibits expression of Myc-responsive CAD and NUC genes, and impairs the Myc-induced S-phase and apoptosis of quiescent cells grown in low serum. Chromatin immunoprecipitation assays (ChIP) demonstrated co-occupancy of Myc and P-TEFb to CAD and NUC E-boxes, and DRB treatment diminished the density of Pol II phosphorylated on Ser-2 of its CTD. These results indicate that P-TEFb is recruited in vivo to Myc-target promoters and CDK9 activity is an important step for Myc-dependent stimulation of responsive genes.

Original languageEnglish
Pages (from-to)2031-2037
Number of pages7
JournalCell Cycle
Volume6
Issue number16
Publication statusPublished - Aug 15 2007

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Keywords

  • c-Myc
  • Cell proliferation
  • ChIP
  • CoIP
  • DRB
  • P-TEFb

ASJC Scopus subject areas

  • Cell Biology
  • Biochemistry
  • Molecular Biology

Cite this

Gargano, B., Amente, S., Majello, B., & Lania, L. (2007). P-TEFb is a crucial co-factor for Myc transactivation. Cell Cycle, 6(16), 2031-2037.