2pz1

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{{STRUCTURE_2pz1| PDB=2pz1 | SCENE= }}
{{STRUCTURE_2pz1| PDB=2pz1 | SCENE= }}
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'''Crystal Structure of Auto-inhibited Asef'''
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===Crystal Structure of Auto-inhibited Asef===
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==Overview==
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Autoinhibition of the Rho guanine nucleotide exchange factor ASEF is relieved by interaction with the APC tumor suppressor. Here we show that binding of the armadillo repeats of APC to a 'core APC-binding' (CAB) motif within ASEF, or truncation of the SH3 domain of ASEF, relieves autoinhibition, allowing the specific activation of CDC42. Structural determination of autoinhibited ASEF reveals that the SH3 domain forms an extensive interface with the catalytic DH and PH domains to obstruct binding and activation of CDC42, and the CAB motif is positioned adjacent to the SH3 domain to facilitate activation by APC. In colorectal cancer cell lines, full-length, but not truncated, APC activates CDC42 in an ASEF-dependent manner to suppress anchorage-independent growth. We therefore propose a model in which ASEF acts as a tumor suppressor when activated by APC and inactivation of ASEF by mutation or APC truncation promotes tumorigenesis.
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{{ABSTRACT_PUBMED_17704816}}
==About this Structure==
==About this Structure==
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[[Category: Helical bundle]]
[[Category: Helical bundle]]
[[Category: Signaling protein]]
[[Category: Signaling protein]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 14:02:46 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 05:58:53 2008''

Revision as of 02:58, 29 July 2008

Image:2pz1.png

Template:STRUCTURE 2pz1

Crystal Structure of Auto-inhibited Asef

Template:ABSTRACT PUBMED 17704816

About this Structure

2PZ1 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Release of autoinhibition of ASEF by APC leads to CDC42 activation and tumor suppression., Mitin N, Betts L, Yohe ME, Der CJ, Sondek J, Rossman KL, Nat Struct Mol Biol. 2007 Sep;14(9):814-23. Epub 2007 Aug 19. PMID:17704816

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