TFIIH core complex helicase subunit XPB (XPB)

TFIIH core complex helicase subunit XPB (ERCC3) is a critical enzymatic component of the multi-subunit TFIIH complex, functioning as a DNA-dependent ATPase and 3'-5' helicase (UniProt). It plays a dual role in cellular maintenance: it is essential for the initiation of RNA polymerase II-mediated transcription by facilitating promoter opening, and it is vital for nucleotide excision repair (NER) by unwinding DNA around bulky lesions (PubMed, NIH). Mutations in the ERCC3 gene are associated with severe autosomal recessive disorders, including Xeroderma pigmentosum group B, Cockayne syndrome, and Trichothiodystrophy, which manifest as extreme UV sensitivity and developmental abnormalities (Wikipedia, NIH). In the context of oncology, XPB is a therapeutic target for the natural product triptolide and its clinical-stage prodrug Minnelide, which covalently bind and inhibit its ATPase activity, leading to global transcription suppression and apoptosis in cancer cells (PubMed, ClinicalTrials.gov). Furthermore, the drug spironolactone has been identified as an inducer of XPB proteasomal degradation, providing a potential mechanism for sensitizing tumors to DNA-damaging therapies (PubMed).

Other names

ERCC3Excision repair cross-complementation group 3BTF2GTF2HRAD25TFIIH core complex helicase subunit XPBTTD2Ssl2Xeroderma pigmentosum group B-complementing protein

Inhibition of ATPase activity; Induction of proteasomal degradation