1muz
From Proteopedia
(New page: 200px<br /> <applet load="1muz" size="450" color="white" frame="true" align="right" spinBox="true" caption="1muz" /> '''NMR STRUCTURE OF THE TUMOR SUPPRESSOR BIN1:...) |
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| - | [[Image:1muz.gif|left|200px]]<br /> | + | [[Image:1muz.gif|left|200px]]<br /><applet load="1muz" size="350" color="white" frame="true" align="right" spinBox="true" |
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caption="1muz" /> | caption="1muz" /> | ||
'''NMR STRUCTURE OF THE TUMOR SUPPRESSOR BIN1: ALTERNATIVE SPLICING IN MELANOMA AND INTERACTION WITH C-MYC'''<br /> | '''NMR STRUCTURE OF THE TUMOR SUPPRESSOR BIN1: ALTERNATIVE SPLICING IN MELANOMA AND INTERACTION WITH C-MYC'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The N terminus of the c-Myc oncoprotein interacts with Bin1, a | + | 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. |
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| + | ==Disease== | ||
| + | Known diseases associated with this structure: Myopathy, centronuclear, autosomal recessive OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=601248 601248]] | ||
==About this Structure== | ==About this Structure== | ||
| - | 1MUZ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http:// | + | 1MUZ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MUZ OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Arrowsmith, C | + | [[Category: Arrowsmith, C H.]] |
[[Category: Pineda-Lucena, A.]] | [[Category: Pineda-Lucena, A.]] | ||
[[Category: tumor suppressor]] | [[Category: tumor suppressor]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:59:23 2008'' |
Revision as of 11:59, 21 February 2008
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NMR STRUCTURE OF THE TUMOR SUPPRESSOR BIN1: ALTERNATIVE SPLICING IN MELANOMA AND INTERACTION WITH C-MYC
Contents |
Overview
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.
Disease
Known diseases associated with this structure: Myopathy, centronuclear, autosomal recessive OMIM:[601248]
About this Structure
1MUZ is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
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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