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PMID: 12198152 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

Timing of APC/C substrate degradation is determined by fzy/fzr specificity of destruction boxes.

The EMBO journal ·Vol. 21 ·No. 17 ·2002-09-02 ·Pages 4500-10

Zur A, Brandeis M

Abstract

The anaphase promoting complex/cyclosome (APC/C), activated by fzy and fzr, degrades cell cycle proteins that carry RXXL or KEN destruction boxes (d-boxes). APC/C substrates regulate sequential events and must be degraded in the correct order during mitosis and G(1). We studied how d-boxes determine APC/C(fzy)/APC/C(fzr) specificity and degradation timing. Cyclin B1 has an RXXL box and is degraded by both APC/C(fzy) and APC/C(fzr); fzy has a KEN box and is degraded by APC/C(fzr) only. We characterized the degradation of substrates with swapped d-boxes. Cyclin B1 with KEN was degraded by APC/C(fzr) only. Fzy with RXXL could be degraded by APC/C(fzy) and APC/C(fzr). Interestingly, APC/C(fzy)- but not APC/C(fzr)-specific degradation is highly dependent on the location of RXXL. We studied degradation of tagged substrates in real time and observed that APC/C(fzr) is activated in early G(1). These observations demonstrate how d-box specificities of APC/C(fzy) and APC/C(fzr), and the successive activation of APC/C by fzy and fzr, establish the temporal degradation pattern. Our observations can explain further why some endogenous RXXL substrates are degraded by APC/C(fzy), while others are restricted to APC/C(fzr).

MeSH Terms
3T3 Cells/metabolism Amino Acid Motifs Amino Acid Sequence Anaphase-Promoting Complex-Cyclosome Animals Antigens, CD Cadherins Cdc20 Proteins Cdh1 Proteins Cell Cycle Proteins/metabolism Cyclin B/chemistry,metabolism Cyclin B1 G1 Phase Humans Ligases/metabolism Macromolecular Substances Mice Molecular Sequence Data Proteins/chemistry,physiology Recombinant Fusion Proteins/metabolism Saccharomyces cerevisiae Proteins/chemistry,physiology Substrate Specificity Time Factors Ubiquitin/metabolism Ubiquitin-Protein Ligase Complexes
Chemicals
Antigens, CD CCNB1 protein, human CDH1 protein, human Cadherins Ccnb1 protein, mouse Cdc20 Proteins Cdc20 protein, mouse Cdh1 Proteins Cell Cycle Proteins Cyclin B Cyclin B1 FZR1 protein, human Fzr1 protein, mouse Macromolecular Substances Proteins Recombinant Fusion Proteins Saccharomyces cerevisiae Proteins Ubiquitin CDC20 protein, human Ubiquitin-Protein Ligase Complexes Anaphase-Promoting Complex-Cyclosome Ligases
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Zur Amit
Department of Genetics, Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, Israel.
Brandeis Michael
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/cdf452
Published
2002-09-02
Pages
4500-10
Language
English
Region
England
NLM ID
8208664
PMCID
PMC126191
Subset
IM
External Links
PubMed source DOI: 10.1093/emboj/cdf452 PMC Full Text View journal details
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