Qiao Feng, Song Haiyun, Kim Chongwoo A, Sawaya Michael R, Hunter Jacob B, Gingery Mari, Rebay Ilaria, Courey Albert J, Bowie James U
UCLA-DOE Institute of Genomics and Proteomics, Molecular Biology Institute, Department of Chemistry and Biochemistry, University of California, Los Angeles 90095, USA.
Cell. 2004 Jul 23;118(2):163-73. 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 approximately 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.
Yan是一种ETS家族转录抑制因子，通过Ras/MAPK途径受受体酪氨酸激酶信号传导调控。一种名为Mae的蛋白质促进了Yan的磷酸化和下调。Yan和Mae通过它们的SAM结构域相互作用。我们发现，Yan的抑制作用需要由Yan-SAM聚合介导形成更高阶结构。此外，Yan-SAM/Mae-SAM复合物的晶体结构表明，Mae-SAM特异性识别Yan-SAM上的一个表面，该表面也是Yan-SAM聚合所必需的。Mae-SAM与Yan-SAM结合的亲和力比Yan-SAM自身结合高约1000倍，并且可以有效地使Yan-SAM解聚。Mae上特异性破坏其与Yan的SAM结构域依赖性相互作用的突变会使Mae在体内的去抑制功能失效。Mae使Yan解聚代表了一种新的转录控制机制，使Yan对受体酪氨酸激酶的调控敏感。
