Preparing your results

Our searching services are busy right now. Your search will reload in five seconds.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

A role for the Fizzy/Cdc20 family of proteins in activation of the APC/C distinct from substrate recruitment.

Molecular cell | Nov 21, 2008

http://www.ncbi.nlm.nih.gov/pubmed/19026787

The Fizzy/Cdc20 family of proteins are essential activators of the anaphase-promoting complex/cyclosome (APC/C), a multisubunit E3 ubiquitin ligase. However, apart from the well-established role of the C-terminal WD40 domain in substrate recognition, the precise roles of the activators remain elusive. Here we show that Nek2A, which directly binds the APC/C, can be ubiquitylated and destroyed in Fizzy/Cdc20-depleted Xenopus egg extracts when only the N-terminal domain of Fizzy/Cdc20 (N-Cdc20) is added. This activity is dependent upon the C box and is conserved in the alternative activator, Fizzy-related/Cdh1. In contrast, canonical substrates such as cyclin B and securin require both the N-terminal and WD40 domains, unless N-Cdc20 is fused to substrates when the WD40 domain becomes dispensable. Furthermore, in Cdc20-depleted cells, N-Cdc20 can facilitate Nek2A destruction in a C box-dependent manner. Our results reveal a role for the N-terminal domain of the Fizzy/Cdc20 family of activators in triggering substrate ubiquitylation by the APC/C.

Pubmed ID: 19026787 RIS Download

Mesh terms: Anaphase-Promoting Complex-Cyclosome | Animals | Cdc20 Proteins | Cell Cycle Proteins | Models, Biological | Protein Structure, Tertiary | Protein-Serine-Threonine Kinases | Proteins | Substrate Specificity | Ubiquitin-Protein Ligase Complexes | Ubiquitination | Xenopus | Xenopus Proteins

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.