Abstract
Human immunodeficiency virus type 1 (HIV-1) Tat is a potent transcriptional activator of the HIV-1 promoter and also has the ability to modulate a number of cellular regulatory circuits including apoptosis. Tat exerts its effects through interaction with viral as well as cellular proteins. Here, we studied the influence of p73, a protein that is implicated in apoptosis and cell cycle control, on Tat functions in the central nervous system. Protein interaction studies using immunoprecipitation followed by Western blot and glutathione S-transferase pull-down assays demonstrated the association of Tat with p73. Tat bound to the N-terminal region of p73 spanning amino acids 1 to 120, and this interaction required the cysteine-rich domain (amino acids 30 to 40) of Tat. Association of p73 with Tat prevented the acetylation of Tat on lysine 28 by PCAF. Functional studies including RNA interference showed that p73 inhibited Tat stimulation of the HIV-1 promoter. Furthermore, p73 prevented the interaction of Tat with cyclin T1 in vitro but not in vivo. These findings suggest possible new therapeutic approaches, using p73, for Tat-mediated AIDS pathogenesis.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Acetylation
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Acetyltransferases / metabolism
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Apoptosis
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Astrocytes / metabolism
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Astrocytes / virology*
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Cell Cycle
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Cell Cycle Proteins / metabolism
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Cell Nucleus / chemistry
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Cell Nucleus / metabolism
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Cells, Cultured
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Central Nervous System / cytology
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Central Nervous System / virology
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Cyclin T
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Cyclins / metabolism
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DNA-Binding Proteins / analysis
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Gene Products, tat / analysis
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Gene Products, tat / genetics
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Gene Products, tat / metabolism*
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Genes, Tumor Suppressor
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HIV-1 / metabolism*
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Histone Acetyltransferases
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Humans
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Immunoprecipitation
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Lysine / metabolism
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Mutation
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Nuclear Proteins / analysis
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism*
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Promoter Regions, Genetic
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Protein Interaction Mapping
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Protein Structure, Tertiary
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RNA Interference
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Transcription Factors / metabolism
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Tumor Protein p73
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Tumor Suppressor Proteins
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p300-CBP Transcription Factors
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tat Gene Products, Human Immunodeficiency Virus
Substances
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CCNT1 protein, human
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Cell Cycle Proteins
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Cyclin T
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Cyclins
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DNA-Binding Proteins
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Gene Products, tat
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Nuclear Proteins
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TP73 protein, human
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Transcription Factors
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Tumor Protein p73
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Tumor Suppressor Proteins
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tat Gene Products, Human Immunodeficiency Virus
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Acetyltransferases
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Histone Acetyltransferases
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p300-CBP Transcription Factors
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p300-CBP-associated factor
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Lysine