The proteasome regulates HIV-1 transcription by both proteolytic and nonproteolytic mechanisms.
Although the proteasome facilitates transcription from several yeast promoters, it is unclear if its role is proteolytic or which subunits are involved. We show that the proteasome regulates the HIV-1 promoter in both proteolytic and nonproteolytic modes. In the absence of transcription factor, Tat, proteasome was associated with promoter and coding regions, and its proteolytic activity regulated the level of basal transcription emanating from the promoter. Tat switched the proteasome to a nonproteolytic mode by recruiting a proteasome-associated protein, PAAF1, which favors proteasome dissociation into 19S and 20S particles. Gel filtration chromatography showed that expression of both Tat and PAAF1 enhanced the abundance of a 19S-like complex in nuclear extracts. 19S, but not 20S, subunits were strongly recruited to the promoter in the presence of Tat and PAAF1 and coactivated Tat-dependent transcription. 19S components facilitated transcriptional elongation and may be involved in clearance of paused transcriptional elongation complexes from the promoter.
Lassot
Irina
I
Laboratoire de Virologie Moléculaire, Institut de Génétique Humaine, Centre National de la Recherche Scientifique UPR1142, Montpellier, France.
Latreille
Daniel
D
Rousset
Emilie
E
Sourisseau
Marion
M
Linares
Laetitia K
LK
Chable-Bessia
Christine
C
Coux
Olivier
O
Benkirane
Monsef
M
Kiernan
Rosemary E
RE
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins / Q000378:metabolism; D015967:Gene Expression Regulation, Viral; D015696:Gene Products, tat / Q000235:genetics / Q000378:metabolism; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D011401:Promoter Regions, Genetic; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D014158:Transcription, Genetic; D054322:tat Gene Products, Human Immunodeficiency Virus
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D015696:Gene Products, tat; C501074:PAAF1 protein, human; D054322:tat Gene Products, Human Immunodeficiency Virus; D046988:Proteasome Endopeptidase Complex; C119011:26S proteasome non-ATPase regulatory subunit 13