Trans-activation of HIV-1 LTR-directed gene expression by tat requires protein kinase C.
Human immunodeficiency virus (HIV) spends a significant part of the viral life cycle as a latent provirus integrated into the host genome. Activation of latent HIV-1 requires mitogenic stimulation of the cell, which increases basal viral transcription, and the HIV-1 tat protein. As tat itself dramatically increases HIV-1 gene expression, it too is presumably regulated in the latent state, and may also be activated by mitogenic stimulation. We show here that depletion of protein kinase C (PKC), which is essential to the stimulation of T cells by several mitogens, dramatically reduces HIV-1 transactivation without affecting synthesis of tat protein. Transactivation in PKC-depleted cells can be restored by transfection with a PKC expression vector. The requirement for PKC in trans-activation does not involve the PMA-responsive enhancer elements responsible for the effect of mitogens on basal transcription. Our results indicate that PKC regulates the process of HIV-1 transactivation, suggesting a key role for the mitogenic induction of trans-activation in the transition of HIV from latency to productive growth.
Jakobovits
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Department of Molecular Biology, Genentech, Inc., South San Francisco, CA 94080.
Rosenthal
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Capon
D J
DJ
D002460:Cell Line; D015967:Gene Expression Regulation, Viral; D015696:Gene Products, tat / Q000378:metabolism*; D005814:Genes, Viral; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D009154:Mutation; D015240:Phorbol 12,13-Dibutyrate / Q000378:metabolism; D010957:Plasmids; D011401:Promoter Regions, Genetic; D011493:Protein Kinase C / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D012091:Repetitive Sequences, Nucleic Acid; D015534:Trans-Activators / Q000378:metabolism*; D015533:Transcriptional Activation; D014162:Transfection; D054322:tat Gene Products, Human Immunodeficiency Virus
D015696:Gene Products, tat; D015534:Trans-Activators; D054322:tat Gene Products, Human Immunodeficiency Virus; D015240:Phorbol 12,13-Dibutyrate; D011493:Protein Kinase C