Alleviation of PC4-mediated transcriptional repression by the ERCC3 helicase activity of general transcription factor TFIIH.
Positive cofactor 4 (PC4), originally identified as a transcriptional coactivator, possesses the ability to suppress promoter-driven as well as nonspecific transcription via its DNA binding activity. Previous studies showed that the repressive activity of PC4 on promoter-driven transcription is alleviated by transcription factor TFIIH, possibly through one of its enzymatic activities. Using recombinant TFIIH, we have analyzed the role of TFIIH for alleviating PC4-mediated transcriptional repression and determined that the excision repair cross complementing (ERCC3) helicase activity of TFIIH is the enzymatic activity that alleviates PC4-mediated repression via beta-gamma bond hydrolysis of ATP. In addition, the alleviation does not require either ERCC2 helicase or cyclin-dependent kinase 7 kinase activity. We also show that, as complexed within TFIIH, the cyclin-dependent kinase 7 kinase does not possess the activity to phosphorylate PC4. Thus, TFIIH appears to protect promoters from PC4-mediated repression by relieving the topological constraint imposed by PC4 through the ERCC3 helicase activity rather than by reducing the repressive activity of PC4 via its phosphorylation.
Fukuda
Aya
A
Department of Molecular Biology, Saitama Medical School, 38 Morohongo, Moroyama, Iruma-gun, Saitama 350-0495, Japan.
Tokonabe
Shigeki
S
Hamada
Mitsuhiro
M
Matsumoto
Masahito
M
Tsukui
Tohru
T
Nogi
Yasuhisa
Y
Hisatake
Koji
K
D000255:Adenosine Triphosphate / Q000378:metabolism; D018844:Cyclin-Dependent Kinases; D004265:DNA Helicases / Q000235:genetics*; D004268:DNA-Binding Proteins; D006801:Humans; D006868:Hydrolysis; D017874:Immediate-Early Proteins; D008565:Membrane Proteins; D009154:Mutation; D010766:Phosphorylation; D011506:Proteins; D011994:Recombinant Proteins; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D051758:Transcription Factor TFIIH; D014157:Transcription Factors; D019473:Transcription Factors, TFII / Q000235:genetics*; D014158:Transcription, Genetic; D051759:Xeroderma Pigmentosum Group D Protein; D000095043:Cyclin-Dependent Kinase-Activating Kinase
D004268:DNA-Binding Proteins; C490043:IFRD2 protein, human; D017874:Immediate-Early Proteins; D008565:Membrane Proteins; D011506:Proteins; D011994:Recombinant Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D019473:Transcription Factors, TFII; C072022:XPBC-ERCC-3 protein; D051758:Transcription Factor TFIIH; D000255:Adenosine Triphosphate; D018844:Cyclin-Dependent Kinases; D004265:DNA Helicases; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human; D000095043:Cyclin-Dependent Kinase-Activating Kinase; C000722416:CDK7 protein, human