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

doi:10.1016/j.cell.2004.07.010

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 journal › Article › peer-review

81 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 language	English (US)
Pages (from-to)	163-173
Number of pages	11
Journal	Cell
Volume	118
Issue number	2
DOIs	https://doi.org/10.1016/j.cell.2004.07.010
State	Published - Jul 23 2004

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)

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10.1016/j.cell.2004.07.010

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title = "Derepression by depolymerization: Structural insights into the regulation of Yan by Mae",

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.",

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

note = "Funding Information: The authors would like to thank Frank Laski for providing the Drosophila cDNA library, Salem Faham and Sarah Yohannan for help with synchrotron data collection, and Aaron Chamberlain, Sehat Nauli, Megan Plotkowski, and Nathan Cho for helpful comments on the manuscript. Fluorescence microscopy was performed at the UCLA/CNSI Advanced Light Microscopy/Spectroscopy Shared Facility. J.U.B. is a Leukemia and Lymphoma Society Scholar. This work was supported by NIH grants R01 CA081000 to J.U.B. and R01 GM44522 to A.J.C. ",

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doi = "10.1016/j.cell.2004.07.010",

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T1 - Derepression by depolymerization

T2 - Structural insights into the regulation of Yan by Mae

AU - Qiao, Feng

AU - Song, Haiyun

AU - Kim, Chongwoo A.

AU - Sawaya, Michael R.

AU - Hunter, Jacob B.

AU - Gingery, Mari

AU - Rebay, Ilaria

AU - Courey, Albert J.

AU - Bowie, James U.

N1 - Funding Information: The authors would like to thank Frank Laski for providing the Drosophila cDNA library, Salem Faham and Sarah Yohannan for help with synchrotron data collection, and Aaron Chamberlain, Sehat Nauli, Megan Plotkowski, and Nathan Cho for helpful comments on the manuscript. Fluorescence microscopy was performed at the UCLA/CNSI Advanced Light Microscopy/Spectroscopy Shared Facility. J.U.B. is a Leukemia and Lymphoma Society Scholar. This work was supported by NIH grants R01 CA081000 to J.U.B. and R01 GM44522 to A.J.C.

PY - 2004/7/23

Y1 - 2004/7/23

N2 - 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.

AB - 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.

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

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