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5ufl

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Revision as of 10:23, 22 November 2017

Crystal structure of a CIP2A core domain

Structural highlights

5ufl is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:	KIAA1524, CIP2A (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[CIP2A_HUMAN] Oncoprotein that inhibits PP2A and stabilizes MYC in human malignancies. Promotes anchorage-independent cell growth and tumor formation.^[1]

Publication Abstract from PubMed

Protein phosphatase 2A (PP2A) is a critical human tumor suppressor. Cancerous inhibitor of PP2A (CIP2A) supports the activity of several critical cancer drivers (Akt, MYC, E2F1) and promotes malignancy in most cancer types via PP2A inhibition. However, the 3D structure of CIP2A has not been solved, and it remains enigmatic how it interacts with PP2A. Here, we show by yeast two-hybrid assays, and subsequent validation experiments, that CIP2A forms homodimers. The homodimerization of CIP2A is confirmed by solving the crystal structure of an N-terminal CIP2A fragment (amino acids 1-560) at 3.0 A resolution, and by subsequent structure-based mutational analyses of the dimerization interface. We further describe that the CIP2A dimer interacts with the PP2A subunits B56alpha and B56gamma. CIP2A binds to the B56 proteins via a conserved N-terminal region, and dimerization promotes B56 binding. Intriguingly, inhibition of either CIP2A dimerization or B56alpha/gamma expression destabilizes CIP2A, indicating opportunities for controlled degradation. These results provide the first structure-function analysis of the interaction of CIP2A with PP2A/B56 and have direct implications for its targeting in cancer therapy.

Oncoprotein CIP2A is stabilized via interaction with tumor suppressor PP2A/B56.,Wang J, Okkeri J, Pavic K, Wang Z, Kauko O, Halonen T, Sarek G, Ojala PM, Rao Z, Xu W, Westermarck J EMBO Rep. 2017 Mar;18(3):437-450. doi: 10.15252/embr.201642788. Epub 2017 Feb 7. PMID:28174209^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Junttila MR, Puustinen P, Niemela M, Ahola R, Arnold H, Bottzauw T, Ala-aho R, Nielsen C, Ivaska J, Taya Y, Lu SL, Lin S, Chan EK, Wang XJ, Grenman R, Kast J, Kallunki T, Sears R, Kahari VM, Westermarck J. CIP2A inhibits PP2A in human malignancies. Cell. 2007 Jul 13;130(1):51-62. PMID:17632056 doi:http://dx.doi.org/10.1016/j.cell.2007.04.044
↑ Wang J, Okkeri J, Pavic K, Wang Z, Kauko O, Halonen T, Sarek G, Ojala PM, Rao Z, Xu W, Westermarck J. Oncoprotein CIP2A is stabilized via interaction with tumor suppressor PP2A/B56. EMBO Rep. 2017 Mar;18(3):437-450. doi: 10.15252/embr.201642788. Epub 2017 Feb 7. PMID:28174209 doi:http://dx.doi.org/10.15252/embr.201642788

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5ufl"

@@ Line 3: / Line 3: @@
 <StructureSection load='5ufl' size='340' side='right' caption='[[5ufl]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5ufl]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5UFL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5UFL FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5ufl]] is a 2 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=5UFL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5UFL FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">KIAA1524, CIP2A ([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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ufl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ufl OCA], [http://pdbe.org/5ufl PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ufl RCSB], [http://www.ebi.ac.uk/pdbsum/5ufl PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ufl ProSAT]</span></td></tr>
 </table>
@@ Line 22: / Line 23: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
 [[Category: Rao, Z]]
 [[Category: Wang, J]]

5ufl

From Proteopedia

Revision as of 10:23, 22 November 2017

Crystal structure of a CIP2A core domain

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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