A Cyclin T1 point mutation that abolishes positive transcription elongation factor (P-TEFb) binding to Hexim1 and HIV tat

Nina Verstraete, Alona Kuzmina, Gaelle Diribarne, Van T. Nguyen, Lydia Kobbi, Monika Ludanyi, Ran Taube, Olivier Bensaude

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


Background: The positive transcription elongation factor b (P-TEFb) plays an essential role in activating HIV genome transcription. It is recruited to the HIV LTR promoter through an interaction between the Tat viral protein and its Cyclin T1 subunit. P-TEFb activity is inhibited by direct binding of its subunit Cyclin T (1 or 2) with Hexim (1 or 2), a cellular protein, bound to the 7SK small nuclear RNA. Hexim1 competes with Tat for P-TEFb binding.Results: Mutations that impair human Cyclin T1/Hexim1 interaction were searched using systematic mutagenesis of these proteins coupled with a yeast two-hybrid screen for loss of protein interaction. Evolutionary conserved Hexim1 residues belonging to an unstructured peptide located N-terminal of the dimerization domain, were found to be critical for P-TEFb binding. Random mutagenesis of the N-terminal region of Cyclin T1 provided identification of single amino-acid mutations that impair Hexim1 binding in human cells. Furthermore, conservation of critical residues supported the existence of a functional Hexim1 homologue in nematodes.Conclusions: Single Cyclin T1 amino-acid mutations that impair Hexim1 binding are located on a groove between the two cyclin folds and define a surface overlapping the HIV-1 Tat protein binding surface. One residue, Y175, in the centre of this groove was identified as essential for both Hexim1 and Tat binding to P-TEFb as well as for HIV transcription.

Original languageEnglish
Article number50
Issue number1
StatePublished - 1 Jul 2014


  • 7SK RNA
  • CDK inhibition
  • Cyclin T
  • Genetic mapping of protein-protein interfaces
  • Hexim1
  • P-TEFb

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases


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