Inhibition of APCCdh1 Activity by Cdh1/Acm1/Bmh1 Ternary Complex Formation

The anaphase-promoting complex (APC) is an essential E3 ubiquitin ligase responsible for catalyzing proteolysis of key regulatory proteins in the cell cycle. Cdh1 is a co-activator of the APC aiding in the onset and maintenance of G1 phase, whereas phosphorylation of Cdh1 at the end of G1 phase by c...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of biological chemistry 2007-02, Vol.282 (8), p.5237-5248
Main Authors: Dial, J. Michael, Petrotchenko, Evgeniy V., Borchers, Christoph H.
Format: Article
Language:English
Subjects:
14-3-3 Proteins
Anaphase - physiology
Cdh1 Proteins
Cell Cycle Proteins
G1 Phase - physiology
Gene Expression
Multiprotein Complexes - genetics
Multiprotein Complexes - metabolism
Phosphorylation
Protein Processing, Post-Translational - physiology
Protein Structure, Quaternary - genetics
Repressor Proteins - genetics
Repressor Proteins - metabolism
Saccharomyces cerevisiae - genetics
Saccharomyces cerevisiae - metabolism
Saccharomyces cerevisiae Proteins - genetics
Saccharomyces cerevisiae Proteins - metabolism
Ubiquitin - genetics
Ubiquitin - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The anaphase-promoting complex (APC) is an essential E3 ubiquitin ligase responsible for catalyzing proteolysis of key regulatory proteins in the cell cycle. Cdh1 is a co-activator of the APC aiding in the onset and maintenance of G1 phase, whereas phosphorylation of Cdh1 at the end of G1 phase by cyclin-dependent kinases assists in the inactivation of APCCdh1. Here, we suggest additional components are involved in the inactivation of APCCdh1 independent of Cdh1 phosphorylation. We have identified proteins known as Acm1 and Bmh1, which bind and form a ternary complex with Cdh1. The presence of phosphorylated Acm1 is critical for the ternary complex formation, and Acm1 is predominantly expressed in S phase when APCCdh1 is inactive. The assembly of the ternary complex inhibits ubiquitination of Clb2 in vitro by blocking the interaction of Cdh1 with Clb2. In vivo, lethality caused by overexpression of constitutively active Cdh1 is rescued by overexpression of Acm1. Partially phosphorylated Cdh1 in the absence of ACM1 still binds to and activates the APC. However, the addition of Acm1 decreases Clb2 ubiquitination when using either phosphorylated or nonphosphorylated Cdh1. Taken together, our results suggest an additional inactivation mechanism exists for APCCdh1 that is independent of Cdh1 phosphorylation.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M606589200