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 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.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence / physiology
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Animals
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Binding Sites / genetics
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Carrier Proteins / chemistry*
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Carrier Proteins / genetics
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Carrier Proteins / metabolism
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Cell Line
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Drosophila
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Drosophila Proteins / chemistry*
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Drosophila Proteins / genetics
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Drosophila Proteins / metabolism
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Eye Proteins / chemistry*
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Eye Proteins / genetics
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Eye Proteins / metabolism
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Genes, Regulator / physiology*
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Humans
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Intracellular Signaling Peptides and Proteins*
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Models, Molecular
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Molecular Structure
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Mutation / genetics
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Polymers / chemistry
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Polymers / metabolism
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Protein Binding / genetics
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Protein Structure, Tertiary / genetics
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Receptor Protein-Tyrosine Kinases / genetics
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Receptor Protein-Tyrosine Kinases / metabolism
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Repressor Proteins / chemistry*
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Repressor Proteins / genetics
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Repressor Proteins / metabolism
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Surface Plasmon Resonance
Substances
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AOP protein, Drosophila
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Carrier Proteins
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Drosophila Proteins
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Eye Proteins
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Intracellular Signaling Peptides and Proteins
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Polymers
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Repressor Proteins
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edl protein, Drosophila
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Receptor Protein-Tyrosine Kinases