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T-loop phosphorylated Cdk9 localizes to nuclear speckle domains which may serve as sites of active P-TEFb function and exchange between the Brd4 and 7SK/HEXIM1 regulatory complexes.

P-TEFb functions to induce the elongation step of RNA polymerase II transcription by phosphorylating the carboxyl-terminal domain of the largest subunit of RNA polymerase II. Core P-TEFb is comprised of Cdk9 and a cyclin regulatory subunit, with Cyclin T1 being the predominant Cdk9-associated cyclin. The kinase activity of P-TEFb is dependent on phosphorylation of the Thr186 residue located within the T-loop domain of the Cdk9 subunit. Here, we used immunofluorescence deconvolution microscopy to examine the subcellular distribution of phospho-Thr186 Cdk9/Cyclin T1 P-TEFb heterodimers. We found that phospho-Thr186 Cdk9 displays a punctate distribution throughout the non-nucleolar nucleoplasm and it co-localizes with Cyclin T1 almost exclusively within nuclear speckle domains. Phospho-Thr186 Cdk9 predominantly co-localized with the hyperphosphorylated forms of RNA polymerase II. Transient expression of kinase-defective Cdk9 mutants revealed that neither is Thr186 phosphorylation or kinase activity required for Cdk9 speckle localization. Lastly, both the Brd4 and HEXIM1 proteins interact with P-TEFb at or very near speckle domains and treatment of cells with the Cdk9 inhibitor flavopiridol alters this distribution. These results indicate that the active form of P-TEFb resides in nuclear speckles and raises the possibility that speckles are sites of P-TEFb function and exchange between negative and positive P-TEFb regulatory complexes.

Pubmed ID: 20201073


  • Dow EC
  • Liu H
  • Rice AP


Journal of cellular physiology

Publication Data

July 30, 2010

Associated Grants

  • Agency: NIAID NIH HHS, Id: AI35381
  • Agency: NIAID NIH HHS, Id: P30 AI036211
  • Agency: NIAID NIH HHS, Id: R56 AI035381
  • Agency: NIAID NIH HHS, Id: R56 AI035381-14A2
  • Agency: NIAID NIH HHS, Id: U54 AI057156
  • Agency: NIAID NIH HHS, Id: U54 AI057156-05S10033

Mesh Terms

  • CD4-Positive T-Lymphocytes
  • Cell Nucleus
  • Cyclin T
  • Cyclin-Dependent Kinase 9
  • Flavonoids
  • HeLa Cells
  • Humans
  • Microscopy, Fluorescence
  • Multienzyme Complexes
  • Mutation
  • Nuclear Proteins
  • Phosphorylation
  • Piperidines
  • Positive Transcriptional Elongation Factor B
  • Protein Kinase Inhibitors
  • Protein Multimerization
  • Protein Transport
  • RNA Polymerase II
  • RNA-Binding Proteins
  • Recombinant Fusion Proteins
  • Ribonucleoproteins, Small Nuclear
  • Threonine
  • Transcription Factors
  • Transcription, Genetic
  • Transfection