PMID:11445587

Citation	Sandrock, B and Egly, JM (2001) A yeast four-hybrid system identifies Cdk-activating kinase as a regulator of the XPD helicase, a subunit of transcription factor IIH. J. Biol. Chem. 276:35328-33
Abstract	To understand the role of the various components of TFIIH, a DNA repair/transcription factor, a yeast four-hybrid system was designed. When the ternary Cdk-activating kinase (CAK) complex composed of Cdk7, cyclin H, and MAT1 was used as bait, the xeroderma pigmentosum (XP) D helicase of transcription factor IIH (TFIIH), among other proteins, was identified as an interacting partner. Deletion mutant analyses demonstrated that the coiled-coil and the hydrophobic domains of MAT1 interlink the CAK complex directly with the N-terminal domain of XPD. Using immunoprecipitates from cells coinfected with baculoviruses, we further validated the bridging function of XPD, which anchors CAK to the core TFIIH. In addition we show that upon interaction with MAT1, CAK inhibits the helicase activity of XPD. This inhibition is overcome upon binding to p44, a subunit of the core TFIIH. It is not surprising that under these conditions some XPD mutations affect interactions not only with p44, but also with MAT1, thus preventing either the CAK inhibitory function within CAK.XPD and/or the role of CAK within TFIIH and, consequently, explaining the variety of the XP phenotypes.
Links	PubMed Online version:10.1074/jbc.M105570200
Keywords	Base Sequence; Cyclin H; Cyclin-Dependent Kinases; Cyclins/metabolism; DNA Helicases/genetics; DNA Helicases/metabolism; DNA Primers; DNA-Binding Proteins; Molecular Probe Techniques; Mutation; Phenotype; Protein-Serine-Threonine Kinases/genetics; Protein-Serine-Threonine Kinases/metabolism; Protein-Serine-Threonine Kinases/physiology; Proteins/genetics; Proteins/metabolism; Transcription Factor TFIIH; Transcription Factors/chemistry; Transcription Factors/metabolism; Transcription Factors, TFII; Xeroderma Pigmentosum Group D Protein
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:ERCC2	part_of	GO:0070516: CAK-ERCC2 complex	ECO:0000314: direct assay evidence used in manual assertion		C		Seeded From UniProt	complete
HUMAN:ERCC2	enables	GO:0043139: 5'-3' DNA helicase activity	ECO:0000314: direct assay evidence used in manual assertion		F		Seeded From UniProt	complete
HUMAN:ERCC2	enables	GO:0005515: protein binding	ECO:0000353: physical interaction evidence used in manual assertion	UniProtKB:P51948	F		Seeded From UniProt	complete
HUMAN:ERCC2	enables	GO:0005515: protein binding	ECO:0000353: physical interaction evidence used in manual assertion	UniProtKB:Q13888	F		Seeded From UniProt	complete
HUMAN:ERCC2	enables	GO:0030674: protein-macromolecule adaptor activity	ECO:0000353: physical interaction evidence used in manual assertion	UniProtKB:P51948,UniProtKB:Q13888	F		Seeded From UniProt	complete
HUMAN:MAT1	part_of	GO:0019907: cyclin-dependent protein kinase activating kinase holoenzyme complex	ECO:0000314: direct assay evidence used in manual assertion		C		Seeded From UniProt	complete
HUMAN:MAT1	involved_in	GO:1905775: negative regulation of DNA helicase activity	ECO:0000314: direct assay evidence used in manual assertion		P	has_input:(UniProtKB:P18074)	Seeded From UniProt	complete
HUMAN:MAT1	enables	GO:0047485: protein N-terminus binding	ECO:0000353: physical interaction evidence used in manual assertion	UniProtKB:P18074	F		Seeded From UniProt	complete
HUMAN:TF2H2	part_of	GO:0000439: transcription factor TFIIH core complex	ECO:0000314: direct assay evidence used in manual assertion		C		Seeded From UniProt	complete
HUMAN:TF2H2	involved_in	GO:1905776: positive regulation of DNA helicase activity	ECO:0000314: direct assay evidence used in manual assertion		P	has_input:(UniProtKB:P18074)	Seeded From UniProt	complete
HUMAN:TF2H2	enables	GO:0005515: protein binding	ECO:0000353: physical interaction evidence used in manual assertion	UniProtKB:P18074	F		Seeded From UniProt	complete

References

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