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Assembly of an APC-Cdh1-substrate complex is stimulated by engagement of a destruction box.

Abstract：

:The anaphase-promoting complex (APC) is a ubiquitin ligase that promotes the degradation of cell-cycle regulators. Cdh1p is an APC coactivator that directly binds APC substrates. A genetic screen in budding yeast identified residues within Cdh1p critical for its function. Cdh1p proteins containing mutations within the "C box" or the "IR" motif could bind substrate, but not the APC, whereas mutants that only bound the APC were not identified, suggesting an ordered assembly of the ternary APC-Cdh1p-substrate complex. Supporting this hypothesis, we found that substrate binding to wild-type Cdh1p enhanced its association with the APC in yeast cells. We used peptide competition assays to demonstrate that Cdh1p interacts directly with the D box and the KEN box, two motifs within APC substrates known to be required for APC-mediated degradation. Moreover, an intact D box domain within a substrate was required to stimulate the association between the Cdh1p-substrate complex and the APC.

journal_name

Mol Cell

journal_title

Molecular cell

authors

Burton JL,Tsakraklides V,Solomon MJ

doi

10.1016/j.molcel.2005.04.022

subject

Has Abstract

pub_date

2005-05-27 00:00:00

pages

533-42

issue

5

eissn

1097-2765

issn

1097-4164

pii

S1097-2765(05)01285-2

journal_volume

18

pub_type

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