Antiapoptotic function of Cdk9 (TAK/P-TEFb) in U937 promonocytic cells.
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.
Foskett
S M
SM
Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas 77030, USA.
Ghose
R
R
Tang
D N
DN
Lewis
D E
DE
Rice
A P
AP
D015703:Antigens, CD / Q000096:biosynthesis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis; D017209:Apoptosis; D015704:CD4 Antigens / Q000032:analysis; D042863:Cyclin-Dependent Kinase 9; D018844:Cyclin-Dependent Kinases / Q000502:physiology*; D015696:Gene Products, tat / Q000502:physiology; D016325:HIV Long Terminal Repeat; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis; D019169:Jurkat Cells; D037181:Lectins, C-Type; D009000:Monocytes / Q000502:physiology*; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015533:Transcriptional Activation; D020298:U937 Cells; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D015704:CD4 Antigens; D042863:Cyclin-Dependent Kinase 9; D018844:Cyclin-Dependent Kinases; D015696:Gene Products, tat; D007376:Interleukin-2; D037181:Lectins, C-Type; D015375:Receptors, Interleukin-2; D013755:Tetradecanoylphorbol Acetate; D000099192:CD69 Antigens; C467969:CDK9 protein, human