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Human Chromosome Segregation Involves Multi-Layered Regulation of Separase by the Peptidyl-Prolyl-Isomerase Pin1

Title data

Hellmuth, Susanne ; Rata, Scott ; Brown, Andreas ; Heidmann, Stefan ; Novak, Bela ; Stemmann, Olaf:
Human Chromosome Segregation Involves Multi-Layered Regulation of Separase by the Peptidyl-Prolyl-Isomerase Pin1.
In: Molecular Cell. Vol. 58 (May 2015) Issue 3 . - pp. 495-506.
ISSN 1097-4164
DOI: https://doi.org/10.1016/j.molcel.2015.03.025

Project information

Project financing: Deutsche Forschungsgemeinschaft

Abstract in another language

Ring-shaped cohesin keeps sister chromatids paired until cleavage of its Scc1/Rad21 subunit by separase triggers chromosome segregation in anaphase. Vertebrate separase is held inactive by mutually exclusive binding to securin or Cdk1-cyclin B1 and becomes unleashed only upon ubiquitin-dependent degradation of these regulators. Although most separase is usually found in association with securin, this anaphase inhibitor is dispensable for murine life while Cdk1-cyclin B1-dependent control of separase is essential. Here, we show that securin-independent inhibition of separase by Cdk1-cyclin B1 in early mitosis requires the phosphorylation-specific peptidyl-prolyl cis/trans isomerase Pin1. Furthermore, isomerization of previously securin-bound separase at the metaphase-to-anaphase transition renders it resistant to re-inhibition by residual securin. At the same time, isomerization also limits the half-life of separase's proteolytic activity, explaining how cohesin can be reloaded onto telophase chromatin in the absence of securin and cyclin B1 without being cleaved.

Further data

Item Type: Article in a journal
Refereed: Yes
Institutions of the University: Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Biology > Chair Genetics > Chair Genetics - Univ.-Prof. Dr. Olaf Stemmann
Result of work at the UBT: Yes
DDC Subjects: 500 Science > 570 Life sciences, biology
Date Deposited: 26 Feb 2020 08:30
Last Modified: 26 Feb 2020 08:31
URI: https://eref.uni-bayreuth.de/id/eprint/54399