|Journal of Molecular Biology (2005) 351(1):182-94|
|Northeast Structural Genomics Consortium|
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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.
|metabolism chemistry genetics |
|Binding Sites Humans Models, Molecular Protein Binding Nuclear Magnetic Resonance, Biomolecular Phosphorylation Carrier Proteins Protein Isoforms Neoplasm Proteins Cell Line Tumor Suppressor Proteins Adaptor Proteins, Signal Transducing Nuclear Proteins Alternative Splicing src Homology Domains Proto-Oncogene Proteins c-myc |
|52 (Last update: 11/17/2018 6:15:13pm)|
|J Mol Biol. 2005 Aug 5;351(1):182-94.|