Transcription intermediary factor 1-beta (TRIM28) (TRIM28/KAP1)

Transcription intermediary factor 1-beta, commonly known as TRIM28 or KAP1, is a multi-domain scaffold protein that serves as a master co-repressor for Kruppel-associated box zinc finger proteins (KRAB-ZFPs) (UniProt Q13263). It functions by recruiting chromatin-modifying enzymes, such as histone deacetylases (HDACs) and the histone methyltransferase SETDB1, to specific genomic loci to induce transcriptional silencing (PubMed: 31434690). Beyond its role in gene regulation, TRIM28 is involved in the DNA damage response through its phosphorylation by ATM at Ser824 and acts as an E3 ubiquitin ligase for proteins like p53 (PubMed: 28232471). In oncology, TRIM28 is frequently overexpressed and correlates with poor prognosis in various cancers, where it promotes epithelial-mesenchymal transition and stemness (PubMed: 33408218). It also plays a critical role in maintaining viral latency for pathogens like HIV-1 and Kaposi's sarcoma-associated herpesvirus (PubMed: 25154350). While no drugs are currently FDA-approved, therapeutic strategies focusing on disrupting its bromodomain or using PROTACs for targeted degradation are under active investigation (PubMed: 33408218).

Other names

KRAB-associated protein 1KAP-1TIF1-betaTripartite motif-containing protein 28KRAB-interacting protein 1RNF96E3 ubiquitin-protein ligase TRIM28

Disruption of the interaction between the KRAB domain and the KAP1 RBCC domain, or inhibition of the KAP1 bromodomain-mediated recruitment of chromatin modifiers (PubMed: 33408218).