Arnold, Lea and Hoeckner, Sebastian and Seufert, Wolfgang (2015) Insights into the cellular mechanism of the yeast ubiquitin ligase APC/C-Cdh1 from the analysis of in vivo degrons. MOLECULAR BIOLOGY OF THE CELL, 26 (5). pp. 843-858. ISSN 1059-1524, 1939-4586
Full text not available from this repository. (Request a copy)Abstract
The anaphase-promoting complex/cyclosome (APC/C) controls a variety of cellular processes through its ability to target numerous protein substrates for timely degradation. Substrate selection by this ubiquitin ligase depends on related activator proteins, Cdc20 and Cdh1, which bind and activate the APC/C at distinct cell cycle stages. Biochemical and structural studies revealed that Cdc20 and Cdh1 carry conserved receptor domains to recognize specific sequence motifs in substrates, such as D and KEN boxes. The mechanisms for ordered degradation of APC/C substrates, however, remain incompletely understood. Here we describe minimal degradation sequences (degrons) sufficient for rapid APC/C-Cdh1-specific in vivo degradation. The polo kinase Cdc5-derived degron contained an essential KEN motif, whereas a single RxxL-type D box was the relevant signal in the Cdc20-derived degradation domain, indicating that either motif may support specific recognition by Cdh1. In both degrons, the APC/C recognition motif was flanked by a nuclear localization sequence. Forced localization of the degron constructs revealed that proteolysis mediated by APC/C-Cdh1 is restricted to the nucleus and maximally active in the nucleoplasm. Levels of Iqg1, a cytoplasmic Cdh1 substrate, decreased detectably later than the nucleus-localized Cdh1 substrate Ase1, indicating that confinement to the nucleus may allow for temporal control of APC/C-Cdh1-mediated proteolysis.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ANAPHASE-PROMOTING-COMPLEX; APC-DEPENDENT PROTEOLYSIS; MITOTIC CYCLIN CLB2; KEN-BOX MOTIFS; SACCHAROMYCES-CEREVISIAE; FLUORESCENT PROTEIN; PHOSPHATASE CDC14; CHROMOSOME ARMS; NUCLEAR EXPORT; S-PHASE; |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Biochemie, Genetik und Mikrobiologie > Cell Cycle Control > Prof. Dr. Wolfgang Seufert |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 24 Jul 2019 11:27 |
| Last Modified: | 24 Jul 2019 11:27 |
| URI: | https://pred.uni-regensburg.de/id/eprint/5871 |
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