Regulation of Transcription Factor SP1 by the β-Catenin Destruction Complex Modulates Wnt Response.

ABSTRACT: The ubiquitous transcription factor specificity protein 1 (SP1) is heavily modified posttranslationally. These modifications are critical for switching its functions and modulation of its transcriptional activity and DNA binding and stability. However, the mechanism governing the stability of SP1 by cellular signaling pathways is not well understood. Here, we provide biochemical and functional evidence that SP1 is an integral part of the Wnt signaling pathway. We identified a phosphodegron motif in SP1 that is specific to mammals. In the absence of Wnt signaling, glycogen synthase kinase 3β (GSK3β)-mediated phosphorylation and β-TrCP E3 ubiquitin ligase-mediated ubiquitination are required to induce SP1 degradation. When Wnt signaling is on, SP1 is stabilized in a β-catenin-dependent manne

SUBMITTER: Mir R 

PROVIDER: S-EPMC6206460 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature