The ubiquitin-proteasome pathway is required for the function of the viral VP16 transcriptional activation domain.
The ability of the activation domain of specific protein factors to regulate transcription is intimately connected to their ubiquitin-mediated proteolysis. Here, we provide evidence that ubiquitin-proteasome function is required for a family of synthetic viral VP16 transcription activators in mammalian cells. Blocking the degradation of VP16 activators, through proteasome inhibitors or by disrupting the ubiquitylation function, severely compromises their transcriptional activity. Overexpression of SUG-1, a subunit of the proteasome, reduces both transactivation and degradation of VP16 activators. The inhibitory effect of SUG-1 overexpression is enhanced when a single non-removable ubiquitin moiety is fused to the amino-terminus of the VP16 activator. The 19S regulatory subunit of the proteasome physically associates with the general transcription factor TFIIH, indicating the direct involvement of the proteasome in transcription. These results support a model in which ubiquitin plays an accessory role, in recruiting the 19S regulatory subunit of the proteasome, for transcriptional activation.
Zhu
Qianzheng
Q
Department of Radiology, The Ohio State University, Columbus, OH 43210, USA.
Yao
Jihong
J
Wani
Gulzar
G
Chen
Jianming
J
Wang
Qi-En
QE
Wani
Altaf A
AA
D000074183:ATPases Associated with Diverse Cellular Activities; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D006367:HeLa Cells; D017405:Herpes Simplex Virus Protein Vmw65 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D060588:LIM Domain Proteins; D007976:Leupeptins / Q000494:pharmacology; D051379:Mice; D009097:Multienzyme Complexes / Q000235:genetics / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D051758:Transcription Factor TFIIH; D014157:Transcription Factors; D019473:Transcription Factors, TFII / Q000378:metabolism; D015533:Transcriptional Activation; D014162:Transfection; D025801:Ubiquitin / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D015853:Cysteine Proteinase Inhibitors; D017405:Herpes Simplex Virus Protein Vmw65; D047908:Intracellular Signaling Peptides and Proteins; D060588:LIM Domain Proteins; D007976:Leupeptins; D009097:Multienzyme Complexes; C092282:PSMC5 protein, human; C491455:Psmc5 protein, mouse; D011993:Recombinant Fusion Proteins; C106843:SUG1 protein, mammalian; D014157:Transcription Factors; D019473:Transcription Factors, TFII; D025801:Ubiquitin; D051758:Transcription Factor TFIIH; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; D000074183:ATPases Associated with Diverse Cellular Activities; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde