Antiapoptotic function of Cdk9 (TAK/P-TEFb) in U937 promonocytic cells

J Virol. 2001 Feb;75(3):1220-8. doi: 10.1128/JVI.75.3.1220-1228.2001.

Abstract

Cdk9 is the catalytic subunit of TAK (cyclinT1/P-TEFb), a cellular protein kinase that mediates human immunodeficiency virus type 1 (HIV-1) Tat transcriptional activation function. To examine Cdk9 function in cells relevant to HIV-1 infection, we used a murine leukemia virus retrovirus vector to transduce and overexpress the cDNA of a dominant negative mutant Cdk9 protein (Cdk9-dn) in Jurkat T cells and U937 promonocytic cells. In Jurkat cells, overexpression of Cdk9-dn specifically inhibited Tat transactivation and HIV-1 replication but had no inhibitory effect on induction of CD69, CD25, and interleukin-2 following T-cell activation. In U937 cells, overexpression of Cdk9-dn sensitized cells to apoptosis, especially after phorbol myristate acetate (PMA) treatment to induce differentiation to macrophage-like cells. Because Cdk9 function is induced in PMA-treated U937 cells, Cdk9 may play an antiapoptotic role during monocyte differentiation.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antigens, CD / biosynthesis
  • Antigens, Differentiation, T-Lymphocyte / biosynthesis
  • Apoptosis*
  • CD4 Antigens / analysis
  • Cyclin-Dependent Kinase 9
  • Cyclin-Dependent Kinases / physiology*
  • Gene Products, tat / physiology
  • HIV Long Terminal Repeat
  • Humans
  • Interleukin-2 / biosynthesis
  • Jurkat Cells
  • Lectins, C-Type
  • Monocytes / physiology*
  • Receptors, Interleukin-2 / biosynthesis
  • Tetradecanoylphorbol Acetate / pharmacology
  • Transcriptional Activation
  • U937 Cells

Substances

  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • CD4 Antigens
  • CD69 antigen
  • Gene Products, tat
  • Interleukin-2
  • Lectins, C-Type
  • Receptors, Interleukin-2
  • CDK9 protein, human
  • Cyclin-Dependent Kinase 9
  • Cyclin-Dependent Kinases
  • Tetradecanoylphorbol Acetate