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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Derepression by depolymerization; structural insights into the regulation of Yan by Mae.

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.[1]


  1. Derepression by depolymerization; structural insights into the regulation of Yan by Mae. Qiao, F., Song, H., Kim, C.A., Sawaya, M.R., Hunter, J.B., Gingery, M., Rebay, I., Courey, A.J., Bowie, J.U. Cell (2004) [Pubmed]
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