Regulation of RIP3 by the transcription factor Sp1 and the epigenetic regulator UHRF1 modulates cancer cell necroptosis.

ABSTRACT: Receptor-interacting kinase-3 (RIP3) is a key regulator of necroptosis. It has been shown that the expression of RIP3 is silenced in most cancer cells and tissues due to genomic methylation. However, the regulatory mechanisms controlling RIP3 expression in cancer cells have not been fully elucidated. Here, we report that Sp1, a well-characterized zinc-finger transcription factor, directly regulates RIP3 expression in cancer cells. Knockdown of endogenous Sp1 significantly decreases the transcription of Rip3, thereby further inhibiting necroptosis. The re-expression of Sp1 restores the necroptotic response. In addition, knockdown of epigenetic regulator UHRF1 (ubiquitin-like, containing PHD and RING finger domains 1) in RIP3-null cancer cells reduces the methylation level of the Rip3 promot

SUBMITTER: Yang C 

PROVIDER: S-EPMC5682651 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature