p73 Interacts with human immunodeficiency virus type 1 Tat in astrocytic cells and prevents its acetylation on lysine 28.
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.
Amini
Shohreh
S
Center for Neurovirology and Cancer Biology, Temple University, 1900 North 12th Street, Philadelphia, PA 19122, USA.
Mameli
Giuseppe
G
Del Valle
Luis
L
Skowronska
Anna
A
Reiss
Krzysztof
K
Gelman
Benjamin B
BB
White
Martyn K
MK
Khalili
Kamel
K
Sawaya
Bassel E
BE
D000107:Acetylation; D000123:Acetyltransferases / Q000378:metabolism; D017209:Apoptosis; D001253:Astrocytes / Q000378:metabolism / Q000821:virology*; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000378:metabolism; D002467:Cell Nucleus / Q000737:chemistry / Q000378:metabolism; D002478:Cells, Cultured; D002490:Central Nervous System / Q000166:cytology / Q000821:virology; D056906:Cyclin T; D016213:Cyclins / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D015696:Gene Products, tat / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D016147:Genes, Tumor Suppressor; D015497:HIV-1 / Q000378:metabolism*; D051548:Histone Acetyltransferases; D006801:Humans; D047468:Immunoprecipitation; D008239:Lysine / Q000378:metabolism; D009154:Mutation; D009687:Nuclear Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D034622:RNA Interference; D014157:Transcription Factors / Q000378:metabolism; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; D050880:p300-CBP Transcription Factors; D054322:tat Gene Products, Human Immunodeficiency Virus; D000099224:p300-CBP-Associated Factor
D000123:Acetyltransferases; D018797:Cell Cycle Proteins; D056906:Cyclin T; D016213:Cyclins; D004268:DNA-Binding Proteins; D015696:Gene Products, tat; D051548:Histone Acetyltransferases; D008239:Lysine; D009687:Nuclear Proteins; D014157:Transcription Factors; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; D050880:p300-CBP Transcription Factors; D054322:tat Gene Products, Human Immunodeficiency Virus; D000099224:p300-CBP-Associated Factor; C503684:CCNT1 protein, human; C000606460:TP73 protein, human