The THAP-Zinc Finger Protein THAP1 Associates with Coactivator HCF-1 andO-GlcNAc Transferase - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue Journal of Biological Chemistry Année : 2010

The THAP-Zinc Finger Protein THAP1 Associates with Coactivator HCF-1 andO-GlcNAc Transferase

Résumé

THAP1 is a sequence-specific DNA binding factor that regulates cell proliferation through modulation of target genes such as the cell cycle-specific gene RRM1. Mutations in the THAP1 DNA binding domain, an atypical zinc finger (THAP-zf), have recently been found to cause DYT6 dystonia, a neurological disease characterized by twisting movements and abnormal postures. In this study, we report that THAP1 shares sequence characteristics, in vivo expression patterns and protein partners with THAP3, another THAP-zf protein. Proteomic analyses identified HCF-1, a potent transcriptional coactivator and cell cycle regulator, and O-GlcNAc transferase (OGT), the enzyme that catalyzes the addition of O-GlcNAc, as major cellular partners of THAP3. THAP3 interacts with HCF-1 through a consensus HCF-1-binding motif (HBM), a motif that is also present in THAP1. Accordingly, THAP1 was found to bind HCF-1 in vitro and to associate with HCF-1 and OGT in vivo. THAP1 and THAP3 belong to a large family of HCF-1 binding factors since seven other members of the human THAP-zf protein family were identified, which harbor evolutionary conserved HBMs and bind to HCF-1. Chromatin immunoprecipitation (ChIP) assays and RNA interference experiments showed that endogenous THAP1 mediates the recruitment of HCF-1 to the RRM1 promoter during endothelial cell proliferation and that HCF-1 is essential for transcriptional activation of RRM1. Together, our findings suggest HCF-1 is an important cofactor for THAP1. Interestingly, our results also provide an unexpected link between DYT6 and DYT3 (X-linked dystonia-parkinsonism) dystonias because the gene encoding the THAP1/DYT6 protein partner OGT maps within the DYT3 critical region on Xq13.1.
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Dates et versions

hal-03107809 , version 1 (12-01-2021)

Identifiants

Citer

Raoul Mazars, Anne Gonzalez-De-Peredo, Corinne Cayrol, Anne-Claire Lavigne, Jodi L Vogel, et al.. The THAP-Zinc Finger Protein THAP1 Associates with Coactivator HCF-1 andO-GlcNAc Transferase: A LINK BETWEEN DYT6 AND DYT3 DYSTONIAS. Journal of Biological Chemistry, 2010, 285 (18), pp.13364 - 13371. ⟨10.1074/jbc.m109.072579⟩. ⟨hal-03107809⟩
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