Disease relevance of GTF2H2

• The gene encoding p44, a subunit of the transcription factor TFIIH, is involved in large-scale deletions associated with Werdnig-Hoffmann disease [1].
• The human xeroderma pigmentosum group B (XPB) helicase is essential for transcription, nucleotide excision repair, and TFIIH functional assembly [2].
• Because transcriptionally generated torsion melts FUSE in vitro even in linear DNA, and FBP/FBP Interacting Repressor (FIR) regulates transcription through TFIIH, these components have been speculated to be the mechanosensor (FUSE) and effectors (FBP/FIR) of a real-time mechanism controlling c-myc transcription [3].
• Screening of deletions in SMN, NAIP and BTF2p44 genes in Turkish spinal muscular atrophy patients [4].
• We conclude that the recruitment and activation of TFIIH represents a rate-limiting step for the emergence of HIV from latency [5].

High impact information on GTF2H2

• In addition, YDR079c-a is a core component of general transcription and DNA repair factor IIH and is required for efficient recruitment of TFIIH to a promoter [6].
• Activation of estrogen receptor alpha by S118 phosphorylation involves a ligand-dependent interaction with TFIIH and participation of CDK7 [7].
• Upon stimulation of the cells by TNF-alpha, NF-kappaB and TFIIH are rapidly recruited to the promoter together with additional Mediator and RNAP II, but CDK8 is lost [5].
• To investigate the role of TFIIH during HIV reactivation in vivo, we developed a population of Jurkat cells containing integrated, but transcriptionally silent, HIV proviruses [5].
• We have compared cells expressing only a mutated p89 (xeroderma pigmentosum complementation group B [XPB]), the largest TFIIH subunit, with the same cells functionally complemented with the wild-type protein (XPB/wt-p89) [8].

Biological context of GTF2H2

• The TFIIH polypeptide composition as well as transcription and DNA repair activities are normal in patients lacking the p44t gene on both mutant chromosomes, suggesting that the p44t gene is not critical for the development of SMA [1].
• We have previously shown that p16(INK4A) inhibits phosphorylation of the CTD by TFIIH [9].
• Participation of XPB/Ptr8p, a component of TFIIH, in nucleocytoplasmic transport of mRNA in fission yeast [10].
• One of these mutations completely inactivates the protein, whereas other TFIIH genes only tolerate point mutations that do not compromise the essential role in transcription [11].
• RNA polymerase II 140wimp mutant and mutations in the TFIIH subunit XPB differentially affect homeotic gene expression in Drosophila [12].

Anatomical context of GTF2H2

• In order to investigate its function, we first described a fast and efficient purification protocol of TFIIH from either HeLa cells or patient cell lines, as well as various in vitro enzymatic assays set up in our laboratory [13].

Other interactions of GTF2H2

• CCNB1 and BTF2p44 were given an exact location [14].
• Three candidate genes, the survival motor neurone (SMN) gene, the neuronal inhibitory protein (NAIP) gene, and the p44 (subunit of basal transcription factor TFIIH) gene, have been considered as genes involved in this condition [15].
• The gene responsible for the TTD-A group of the DNA repair deficient disease trichothiodystrophy has been identified as a small, 8 kDa, component of the transcription factor TFIIH which contributes to the stability and concentration of TFIIH in vivo [16].
• Transcription/repair factor IIH (TFIIH) is essential for RNA polymerase II transcription and nucleotide excision repair (NER) [11].

Analytical, diagnostic and therapeutic context of GTF2H2

• The results obtained from our immunoprecipitation experiment further demonstrated that the ATM protein interacted with the TFIIH basal transcription factor and the XPG protein of the NER pathway [17].

References