|
|
| (One intermediate revision not shown.) |
| Line 1: |
Line 1: |
| | | | |
| | ==Solution structure of the Orange domain from human protein HES1== | | ==Solution structure of the Orange domain from human protein HES1== |
| - | <StructureSection load='7c4o' size='340' side='right'caption='[[7c4o]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='7c4o' size='340' side='right'caption='[[7c4o]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[7c4o]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7C4O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7C4O FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7c4o]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7C4O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7C4O FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HES1, BHLHB39, HL, HRY ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | </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=7c4o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7c4o OCA], [https://pdbe.org/7c4o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7c4o RCSB], [https://www.ebi.ac.uk/pdbsum/7c4o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7c4o ProSAT]</span></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=7c4o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7c4o OCA], [https://pdbe.org/7c4o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7c4o RCSB], [https://www.ebi.ac.uk/pdbsum/7c4o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7c4o ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/HES1_HUMAN HES1_HUMAN]] Transcriptional repressor of genes that require a bHLH protein for their transcription. May act as a negative regulator of myogenesis by inhibiting the functions of MYOD1 and ASH1. Binds DNA on N-box motifs: 5'-CACNAG-3' with high affinity and on E-box motifs: 5'-CANNTG-3' with low affinity (By similarity). May play a role in a functional FA core complex response to DNA cross-link damage, being required for the stability and nuclear localization of FA core complex proteins, as well as for FANCD2 monoubiquitination in response to DNA damage.<ref>PMID:18550849</ref>
| + | [https://www.uniprot.org/uniprot/HES1_HUMAN HES1_HUMAN] Transcriptional repressor of genes that require a bHLH protein for their transcription. May act as a negative regulator of myogenesis by inhibiting the functions of MYOD1 and ASH1. Binds DNA on N-box motifs: 5'-CACNAG-3' with high affinity and on E-box motifs: 5'-CANNTG-3' with low affinity (By similarity). May play a role in a functional FA core complex response to DNA cross-link damage, being required for the stability and nuclear localization of FA core complex proteins, as well as for FANCD2 monoubiquitination in response to DNA damage.<ref>PMID:18550849</ref> |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | Herein, we report that hairy and enhancer of split homolog-1 (HES1), known to repress gene transcription in progenitor cells of several cell lineages, is strongly expressed in cells and tissues of T-cell lymphoma expressing the oncogenic chimeric tyrosine kinase nucleophosmin (NPM)-anaplastic lymphoma kinase [ALK; ALK(+) T-cell lymphoma (TCL)]. The structure analysis of the Orange domain of HES1 indicates that HES1 forms a highly stable homodimer. Of note, repression of HES1 expression leads to inhibition of ALK(+) TCL cell growth in vivo. The expression of the HES1 gene is induced by NPM-ALK through activation of STAT3, which binds to the gene's promoter and induces the gene's transcription. NPM-ALK also directly phosphorylates HES1 protein. In turn, HES1 up-regulates and down-regulates in ALK(+) TCL cell expression of numerous genes, protein products of which are involved in key cell functions, such as cell proliferation and viability. Among the genes inhibited by HES1 is thioredoxin-interacting protein (TXNIP), encoding a protein implicated in promotion of cell death in various types of cells. Accordingly, ALK(+) TCL cells and tissues lack expression of TXNIP, and its transcription is co-inhibited by HES1 and STAT3 in an NPM-ALK-dependent manner. Finally, the induced expression of TXNIP induces massive apoptotic cell death of ALK(+) TCL cells. The results revealed a novel NPM-ALK-controlled pro-oncogenic regulatory network and document an important role of HES and TXNIP in the NPM-ALK-driven oncogenesis, with the former protein displaying oncogenic and the latter tumor suppressor properties.
| + | |
| - | | + | |
| - | Induction of Transcriptional Inhibitor Hairy and Enhancer of Split Homolog-1 and the Related Repression of Tumor-Suppressor Thioredoxin-Interacting Protein Are Important Components of Cell-Transformation Program Imposed by Oncogenic Kinase Nucleophosmin-Anaplastic Lymphoma Kinase.,Zhang Q, Wang HY, Nayak A, Nunez-Cruz S, Slupianek A, Liu X, Basappa J, Fan JS, Chekol S, Nejati R, Bogusz AM, Turner SD, Swaminathan K, Wasik MA Am J Pathol. 2022 May 28. pii: S0002-9440(22)00148-1. doi:, 10.1016/j.ajpath.2022.05.005. PMID:35640677<ref>PMID:35640677</ref>
| + | |
| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 7c4o" style="background-color:#fffaf0;"></div>
| + | |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Fan, J S]] | + | [[Category: Fan JS]] |
| - | [[Category: Nayak, A]] | + | [[Category: Nayak A]] |
| - | [[Category: Swaminathan, K]] | + | [[Category: Swaminathan K]] |
| - | [[Category: Dimer]]
| + | |
| - | [[Category: Signaling protein]]
| + | |
| - | [[Category: Solution structure]]
| + | |
