Transcription initiation factor TFIID subunit 12 (TAF12) histone-fold domain (TAF12)

Transcription initiation factor TFIID subunit 12 (TAF12) is a vital component of the TFIID and SAGA complexes, which are essential for RNA polymerase II-mediated transcription initiation (UniProt P30659). The protein is characterized by its C-terminal histone-fold domain (HFD), which mediates crucial protein-protein interactions, most notably heterodimerization with TAF4 to form a stable structural core within TFIID (PubMed: 27041226). In the context of disease, TAF12 has been identified as a key co-activator for the MYB oncogene in acute myeloid leukemia (AML), where its HFD interacts with MYB to drive an oncogenic transcriptional program (PubMed: 26878235). This interaction makes the TAF12 HFD a significant therapeutic target, as disrupting its binding to MYB or TAF4 can selectively impair the survival of leukemic cells. While no drugs are currently FDA-approved, experimental small molecules and peptidomimetics are being developed to target these specific HFD-mediated interactions to treat MYB-dependent cancers and other malignancies (PubMed: 30104378).

Other names

TAFII20TAF2JTranscription initiation factor TFIID 20 kDa subunitTAFII-20

Inhibition of protein-protein interactions (PPI) involving the histone-fold domain, specifically disrupting the TAF12-TAF4 or TAF12-MYB complexes (PubMed: 26878235, PubMed: 30104378).