1mv3
NMR STRUCTURE OF THE TUMOR SUPPRESSOR BIN1: ALTERNATIVE SPLICING IN MELANOMA AND INTERACTION WITH C-MYC
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OverviewOverview
The N terminus of the c-Myc oncoprotein interacts with Bin1, a, ubiquitously expressed nucleocytoplasmic protein with features of a tumor, suppressor. The c-Myc/Bin1 interaction is dependent on the highly, conserved Myc Box 1 (MB1) sequence of c-Myc. The c-Myc/Bin1 interaction, has potential regulatory significance as c-Myc-mediated transformation and, apoptosis can be modulated by the expression of Bin1. Multiple splicing of, the Bin1 transcript results in ubiquitous, tissue-specific and, tumor-specific populations of Bin1 proteins in vivo. We report on the, structural features of the interaction between c-Myc and Bin1, and, describe two mechanisms by which the binding of different Bin1 isoforms to, c-Myc may be regulated in cells. Our findings identify a consensus class, II SH3-binding motif in c-Myc and the C-terminal SH3 domain of Bin1 as the, primary structure determinants of their interaction. We present, biochemical and structural evidence that tumor-specific isoforms of Bin1, are precluded from interaction with c-Myc through an intramolecular, polyproline-SH3 domain interaction that inhibits the Bin1 SH3 domain from, binding to c-Myc. Furthermore, c-Myc/Bin1 interaction can be inhibited by, phosphorylation of c-Myc at Ser62, a functionally important residue found, within the c-Myc SH3-binding motif. Our data provide a structure-based, model of the c-Myc/Bin1 interaction and suggest a mode of regulation that, may be important for c-Myc function as a regulator of gene transcription.
About this StructureAbout this Structure
1MV3 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
A structure-based model of the c-Myc/Bin1 protein interaction shows alternative splicing of Bin1 and c-Myc phosphorylation are key binding determinants., Pineda-Lucena A, Ho CS, Mao DY, Sheng Y, Laister RC, Muhandiram R, Lu Y, Seet BT, Katz S, Szyperski T, Penn LZ, Arrowsmith CH, J Mol Biol. 2005 Aug 5;351(1):182-94. PMID:15992821
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