1mv3: Difference between revisions
New page: left|200px<br /> <applet load="1mv3" size="450" color="white" frame="true" align="right" spinBox="true" caption="1mv3" /> '''NMR STRUCTURE OF THE TUMOR SUPPRESSOR BIN1:... |
No edit summary |
||
| Line 1: | Line 1: | ||
[[Image:1mv3. | [[Image:1mv3.jpg|left|200px]]<br /><applet load="1mv3" size="350" color="white" frame="true" align="right" spinBox="true" | ||
<applet load="1mv3" size=" | |||
caption="1mv3" /> | caption="1mv3" /> | ||
'''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 /> | ||
| Line 6: | Line 5: | ||
==Overview== | ==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. | 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:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=601248 601248]] | |||
==About this Structure== | ==About this Structure== | ||
1MV3 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:// | 1MV3 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=1MV3 OCA]. | ||
==Reference== | ==Reference== | ||
| Line 18: | Line 20: | ||
[[Category: tumor suppressor]] | [[Category: tumor suppressor]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 16:25:58 2008'' | ||
