Functional Disruption of Gli1-DNA Recognition via a Cobalt(III) Complex.

ABSTRACT: The aberrant activation of the Gli family of zinc finger transcription factors (ZFTFs) is associated with several types of human cancer, including medulloblastoma and basal cell carcinoma. We have reported the use of cobalt(III) Schiff-base complexes (Co(III)-sb) as potent inhibitors of ZFTFs in vivo. These complexes inhibit transcription by displacing the zinc finger domain's structural Zn(II) ion, destabilizing the alpha helix necessary for DNA recognition. Here, we describe the use of Co(III)-sb complexes for the selective inhibition of Gli1. Spectroscopic and computational studies of the Gli1 DNA binding domain found that Co(III)-sb displaced Zn(II) through direct coordination with the His residues of the Cys₂ His₂ Zn(II) binding site. As a result, there is a dose

SUBMITTER: Brue CR 

PROVIDER: S-EPMC10826845 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature