Binding and transcriptional regulation by 14-3-3 (Bmh) proteins requires residues outside of the canonical motif

Pabitra K. Parua, Elton T. Young

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Evolutionarily conserved 14-3-3 proteins have important functions as dimers in numerous cellular signaling processes, including regulation of transcription. Yeast 14-3-3 proteins, known as Bmh, inhibit a post-DNA binding step in transcription activation by Adr1, a glucose-regulated transcription factor, by binding to its regulatory domain, residues 226 to 240. The domain was originally defined by regulatory mutations, ADR1c alleles that alter activator-dependent gene expression. Here, we report that ADR1c alleles and other mutations in the regulatory domain impairBmhbinding and abolish Bmh-dependent regulation both directly and indirectly. The indirect effect is caused by mutations that inhibit phosphorylation of Ser230 and thus inhibitBmhbinding, which requires phosphorylated Ser230. However, several mutations inhibitBmhbinding without inhibiting phosphorylation and thus define residues that provide important interaction sites between Adr1 and Bmh. Our proposed model of the Adr1 regulatory domain bound toBmhsuggests that residues Ser238 and Tyr239 could provide cross-dimer contacts to stabilize the complex and that this might explain the failure of a dimerization-deficientBmhmutant to bind Adr1 and to inhibit its activity. A bioinformatics analysis of Bmh-interacting proteins suggests that residues outside the canonical 14-3-3 motif might be a general property ofBmhtarget proteins and might help explain the ability of 14-3-3 to distinguish target and nontarget proteins.Bmhbinding to the Adr1 regulatory domain, and its failure to bind when mutations are present, explains at a molecular level the transcriptional phenotype of ADR1c mutants.

Original languageEnglish (US)
Pages (from-to)21-30
Number of pages10
JournalEukaryotic Cell
Volume13
Issue number1
DOIs
StatePublished - Jan 2014
Externally publishedYes

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology

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