General transcription factor IIH subunit 3 (GTF2H3) (GTF2H3)

General transcription factor IIH subunit 3 (GTF2H3), also known as p34, is a core component of the multi-subunit TFIIH complex, which is essential for both RNA polymerase II-mediated transcription and nucleotide excision repair (NER) (UniProt Q13889). Within the TFIIH core, GTF2H3 interacts with other subunits like p44 (GTF2H2) to provide structural stability and facilitate the assembly of the holoenzyme required for promoter opening and escape (GeneCards; NIH). Dysregulation of GTF2H3 and the TFIIH complex is associated with various cancers, including endometrial and bladder cancer, as well as genetic repair disorders like Cockayne syndrome and xeroderma pigmentosum (Wikipedia). Because cancer cells often exhibit "transcriptional addiction," the TFIIH complex has emerged as a significant therapeutic target (NIH). While most current inhibitors like triptolide and THZ1 target the enzymatic subunits XPB and CDK7 respectively, GTF2H3 is a critical structural node whose disruption can lead to complex instability and cell death (NIH; Open Targets). Consequently, targeting the protein-protein interactions of GTF2H3 represents a potential strategy for developing novel anti-cancer agents that induce global transcriptional collapse in malignant cells.

Other names

TFIIH subunit 3p34BTF2 p34General transcription factor IIH polypeptide 3TFB4

Inhibition of the TFIIH complex, leading to the suppression of RNA polymerase II-mediated transcription and nucleotide excision repair.