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

作者：Qiao F; Song HY; Kim CA; Sawaya MR; Hunter JB; Gingery M; Rebay I; Courey AJ; Bowie JU^*

来源：Cell, 2004, 118(2): 163-173.

DOI：10.1016/j.cell.2004.07.010

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 similar to1000-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.

• 出版日期2004-7-23
• 单位MIT