Derepression by depolymerization: Structural insights into the regulation of Yan by Mae

Feng Qiao, Haiyun Song, Chongwoo A. Kim, Michael R. Sawaya, Jacob B. Hunter, Mari Gingery, Ilaria Rebay, Albert J. Courey, James U. Bowie

Research output: Contribution to journalArticlepeer-review

74 Scopus citations

Abstract

Yan, an ETS family transcriptional repressor, is regulated by receptor tyrosine kinase signaling via the Ras/MAPK pathway. Phosphorylation and downregulation of Yan is facilitated by a protein called Mae. Yan and Mae interact through their SAM domains. We find that repression by Yan requires the formation of a higher order structure mediated by Yan-SAM polymerization. Moreover, a crystal structure of the Yan-SAM/Mae-SAM complex shows that Mae-SAM specifically recognizes a surface on Yan-SAM that is also required for Yan-SAM polymerization. Mae-SAM binds to Yan-SAM with ∼1000-fold higher affinity than Yan-SAM binds to itself and can effectively depolymerize Yan-SAM. Mutations on Mae that specifically disrupt its SAM domain-dependent interactions with Yan disable the derepression function of Mae in vivo. Depolymerization of Yan by Mae represents a novel mechanism of transcriptional control that sensitizes Yan for regulation by receptor tyrosine kinases.

Original languageEnglish (US)
Pages (from-to)163-173
Number of pages11
JournalCell
Volume118
Issue number2
DOIs
StatePublished - Jul 23 2004

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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