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PP2A delays APC/C-dependent degradation of separase-associated but not free securin

Title data

Hellmuth, Susanne ; Böttger, Franziska ; Pan, Cuiping ; Mann, Matthias ; Stemmann, Olaf:
PP2A delays APC/C-dependent degradation of separase-associated but not free securin.
In: The EMBO Journal. Vol. 33 (16 May 2014) Issue 10 . - pp. 1134-1147.
ISSN 0261-4189
DOI: https://doi.org/10.1002/embj.201488098

Official URL: Volltext

Abstract in another language

The universal triggering event of eukaryotic chromosome segregation is cleavage of centromeric cohesin by separase. Prior to anaphase, most separase is kept inactive by association with securin. Protein phosphatase 2A (PP2A) constitutes another binding partner of human separase, but the functional relevance of this interaction has remained enigmatic. We demonstrate that PP2A stabilizes separase-associated securin by dephosphorylation, while phosphorylation of free securin enhances its polyubiquitylation by the ubiquitin ligase APC/C and proteasomal degradation. Changing PP2A substrate phosphorylation sites to alanines slows degradation of free securin, delays separase activation, lengthens early anaphase, and results in anaphase bridges and DNA damage. In contrast, separase-associated securin is destabilized by introduction of phosphorylation-mimetic aspartates or extinction of separase-associated PP2A activity. G2- or prometaphase-arrested cells suffer from unscheduled activation of separase when endogenous securin is replaced by aspartate-mutant securin. Thus, PP2A-dependent stabilization of separase-associated securin prevents precocious activation of separase during checkpoint-mediated arrests with basal APC/C activity and increases the abruptness and fidelity of sister chromatid separation in anaphase.

Further data

Item Type: Article in a journal
Refereed: Yes
Keywords: APC/C; PP2A; securin; separase; ubiquitylation
Institutions of the University: Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Biology > Chair Genetics > Chair Genetics - Univ.-Prof. Dr. Olaf Stemmann
Profile Fields > Advanced Fields > Molecular Biosciences
Research Institutions > Research Centres > Bayreuth Center for Molecular Biosciences - BZMB
Faculties
Faculties > Faculty of Biology, Chemistry and Earth Sciences
Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Biology
Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Biology > Chair Genetics
Profile Fields
Profile Fields > Advanced Fields
Research Institutions
Research Institutions > Research Centres
Result of work at the UBT: Yes
DDC Subjects: 500 Science > 570 Life sciences, biology
Date Deposited: 26 Mar 2015 07:43
Last Modified: 09 Mar 2016 05:59
URI: https://eref.uni-bayreuth.de/id/eprint/8275