Transcription factor II H subunit XPB (XPB) (XPB)

Transcription factor II H subunit XPB (XPB), encoded by the ERCC3 gene, is an essential component of the ten-subunit TFIIH complex [5, 10]. It functions as an ATP-dependent 3'-5' DNA helicase and ATPase, playing a dual role in RNA polymerase II-mediated transcription initiation and nucleotide excision repair (NER) [1, 9]. In transcription, XPB is responsible for promoter opening and escape, while in NER, it helps unwind DNA around bulky lesions to facilitate repair [7, 11]. Mutations in XPB are associated with severe genetic disorders, including xeroderma pigmentosum group B, Cockayne syndrome, and trichothiodystrophy [5, 14]. XPB has gained significant interest as a therapeutic target in oncology, particularly for the natural product triptolide and its derivatives like Minnelide [2, 13]. Triptolide covalently binds to the Cys342 residue of XPB, inhibiting its ATPase activity and leading to global transcriptional repression and induction of apoptosis, especially in MYC-amplified cancers [1, 4, 13].

Other names

ERCC3BTF2GTF2HRAD25Xeroderma pigmentosum group B complementing proteinTFIIH 89 kDa subunit

Covalent inhibition of the ATPase activity of XPB, leading to global inhibition of RNA polymerase II-mediated transcription and nucleotide excision repair [1, 2].