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| | ==PTB domain of human Numb isoform-1== | | ==PTB domain of human Numb isoform-1== |
| - | <StructureSection load='5njk' size='340' side='right' caption='[[5njk]], [[Resolution|resolution]] 3.13Å' scene=''> | + | <StructureSection load='5njk' size='340' side='right'caption='[[5njk]], [[Resolution|resolution]] 3.13Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5njk]] is a 12 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5NJK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5NJK FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5njk]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5NJK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5NJK FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.13Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NUMB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5njk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5njk OCA], [https://pdbe.org/5njk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5njk RCSB], [https://www.ebi.ac.uk/pdbsum/5njk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5njk ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5njk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5njk OCA], [http://pdbe.org/5njk PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5njk RCSB], [http://www.ebi.ac.uk/pdbsum/5njk PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5njk ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/NUMB_HUMAN NUMB_HUMAN]] Plays a role in the process of neurogenesis. Required throughout embryonic neurogenesis to maintain neural progenitor cells, also called radial glial cells (RGCs), by allowing their daughter cells to choose progenitor over neuronal cell fate. Not required for the proliferation of neural progenitor cells before the onset of neurogenesis. Also involved postnatally in the subventricular zone (SVZ) neurogenesis by regulating SVZ neuroblasts survival and ependymal wall integrity. May also mediate local repair of brain ventricular wall damage. | + | [https://www.uniprot.org/uniprot/NUMB_HUMAN NUMB_HUMAN] Plays a role in the process of neurogenesis. Required throughout embryonic neurogenesis to maintain neural progenitor cells, also called radial glial cells (RGCs), by allowing their daughter cells to choose progenitor over neuronal cell fate. Not required for the proliferation of neural progenitor cells before the onset of neurogenesis. Also involved postnatally in the subventricular zone (SVZ) neurogenesis by regulating SVZ neuroblasts survival and ependymal wall integrity. May also mediate local repair of brain ventricular wall damage. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Fiore, P P.Di]] | + | [[Category: Large Structures]] |
| - | [[Category: Mapelli, M]] | + | [[Category: Di Fiore PP]] |
| - | [[Category: Breast cancer]] | + | [[Category: Mapelli M]] |
| - | [[Category: Endocytosis]]
| + | |
| - | [[Category: Numb]]
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| - | [[Category: Ptb domain]]
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| Structural highlights
Function
NUMB_HUMAN Plays a role in the process of neurogenesis. Required throughout embryonic neurogenesis to maintain neural progenitor cells, also called radial glial cells (RGCs), by allowing their daughter cells to choose progenitor over neuronal cell fate. Not required for the proliferation of neural progenitor cells before the onset of neurogenesis. Also involved postnatally in the subventricular zone (SVZ) neurogenesis by regulating SVZ neuroblasts survival and ependymal wall integrity. May also mediate local repair of brain ventricular wall damage.
Publication Abstract from PubMed
Numb functions as an oncosuppressor by inhibiting Notch signaling and stabilizing p53. This latter effect depends on the interaction of Numb with Mdm2, the E3 ligase that ubiquitinates p53 and commits it to degradation. In breast cancer (BC), loss of Numb results in a reduction of p53-mediated responses including sensitivity to genotoxic drugs and maintenance of homeostasis in the stem cell compartment. In this study, we show that the Numb-Mdm2 interaction represents a fuzzy complex mediated by a short Numb sequence encompassing its alternatively spliced exon 3 (Ex3), which is necessary and sufficient to inhibit Mdm2 and prevent p53 degradation. Alterations in the Numb splicing pattern are critical in BC as shown by increased chemoresistance of tumors displaying reduced levels of Ex3-containing isoforms, an effect that could be mechanistically linked to diminished p53 levels. A reduced level of Ex3-less Numb isoforms independently predicts poor outcome in BCs harboring wild-type p53. Thus, we have uncovered an important mechanism of chemoresistance and progression in p53-competent BCs.
A Numb-Mdm2 fuzzy complex reveals an isoform-specific involvement of Numb in breast cancer.,Colaluca IN, Basile A, Freiburger L, D'Uva V, Disalvatore D, Vecchi M, Confalonieri S, Tosoni D, Cecatiello V, Malabarba MG, Yang CJ, Kainosho M, Sattler M, Mapelli M, Pece S, Di Fiore PP J Cell Biol. 2017 Dec 21. pii: jcb.201709092. doi: 10.1083/jcb.201709092. PMID:29269425[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Colaluca IN, Basile A, Freiburger L, D'Uva V, Disalvatore D, Vecchi M, Confalonieri S, Tosoni D, Cecatiello V, Malabarba MG, Yang CJ, Kainosho M, Sattler M, Mapelli M, Pece S, Di Fiore PP. A Numb-Mdm2 fuzzy complex reveals an isoform-specific involvement of Numb in breast cancer. J Cell Biol. 2017 Dec 21. pii: jcb.201709092. doi: 10.1083/jcb.201709092. PMID:29269425 doi:http://dx.doi.org/10.1083/jcb.201709092
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