HIV-Tat protein activates c-Jun N-terminal kinase and activator protein-1.
Human immunodeficiency virus-1 tat (HIV-tat) protein, like other proinflammatory cytokines (such as TNF), activates a wide variety of cellular responses, some of which play a critical role in progression of HIV infection. Whether HIV-tat, like TNF, also activates c-Jun N-terminal kinase (JNK) and the transcription factor activator protein (AP)-1 is not known. We show that treatment of human histiocytic lymphoma U937 cells with the HIV-tat protein causes activation of JNK and AP-1 in a time- and dose-dependent manner. Transfection of a T cell line, H9 cells with the HIV-tat gene also resulted in an activation of JNK that was not further increased by treatment of cells with exogenous HIV-tat protein. Neutralizing Ab against HIV-tat inhibited the HIV-tat-mediated JNK activation. The activation of JNK by HIV-tat appears to be mediated through generation of free radical species, since pretreatment of cells with N-acetylcysteine (NAC) abolished the effect. Overall our results demonstrate that HIV-tat activates JNK and AP-1, which may contribute to the pathogenesis of AIDS.
Department of Molecular Oncology, University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
A
A
Kumar
S K
SK
Manna
S
S
Dhawan
B B
BB
Aggarwal
D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002460:Cell Line; D004789:Enzyme Activation / Q000187:drug effects / Q000276:immunology; D005609:Free Radicals / Q000276:immunology / Q000378:metabolism; D015696:Gene Products, tat / Q000235:genetics / Q000494:pharmacology* / Q000502:physiology; D015756:Genes, tat / Q000276:immunology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D019169:Jurkat Cells; D007700:Kinetics; D020929:Mitogen-Activated Protein Kinase Kinases; D020928:Mitogen-Activated Protein Kinases; D011494:Protein Kinases / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014162:Transfection / Q000276:immunology; D054322:tat Gene Products, Human Immunodeficiency Virus
D005609:Free Radicals; D015696:Gene Products, tat; D018808:Transcription Factor AP-1; D054322:tat Gene Products, Human Immunodeficiency Virus; D011494:Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases