View source for 7qrs


==Structural insight into the Scribble PDZ domains interaction with the oncogenic Human T-cell lymphotrophic virus-1 (HTLV-1) Tax1==
<StructureSection load='7qrs' size='340' side='right'caption='[[7qrs]], [[Resolution|resolution]] 1.77&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7qrs]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Human_T-cell_leukemia_virus_type_I Human T-cell leukemia virus type I]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7QRS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7QRS FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.77&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></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=7qrs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7qrs OCA], [https://pdbe.org/7qrs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7qrs RCSB], [https://www.ebi.ac.uk/pdbsum/7qrs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7qrs ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/TAX_HTL1C TAX_HTL1C] Transcriptional activator that activates both the viral long terminal repeat (LTR) and cellular promoters via activation of CREB, NF-kappa-B, SRF and AP-1 pathways. Binds to three 21 bp repeat elements located within the LTRs, referred to as Tax-responsive elements (TRE). Binding to TRE requires the interaction with CREB1 and CREBBP. Also induces chromatin remodeling of proviral LTR-mediated gene expression by recruiting the histone acetyl transferases CREBBP and EP300 to the chromatin, which results in histone acetylation. Via its interaction with IKK regulatory subunit IKBKG, Tax-1 persistently stimulates I-kappa-B kinase (IKK), resulting in constitutive activation of the transcription factor NF-kappa-B. Induction of the nuclear expression of members of the NFkB family of transcription factors, which leads to up-regulated expression of many gene promoters containing NFkB motifs. These genes include those encoding IL2, IL15, IL2RA and IL15RA, leading to autocrine IL2/IL2RA and IL15/IL15RA loops. The resulting T-cell proliferation leads to malignant transformation and to the development of adult T-cell leukemia (ATL). IL13, known to be linked to leukemogenesis, is also up-regulated by Tax-1. Interaction with PDZ domain-containing proteins induce IL2-independent growth, which may be a factor in multi-step leukemogenesis. Inhibits the action of at least three cellular tumor suppressors p53/TP53, RB1 and DLG1, and suppresses their abilities to dictate apoptosis in primary cells. Required for viral replication (By similarity).
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Human T-cell leukemia virus type I]]
[[Category: Large Structures]]
[[Category: Humbert PO]]
[[Category: Javorsky A]]
[[Category: Kvansakul M]]
[[Category: Mackie ER]]
[[Category: Soares da Costa TP]]