Deciphering the modes of human separase inhibition by securin and CDK1-CCNB1

Mol Cell Oncol. 2021 Sep 24;8(4):1975473. doi: 10.1080/23723556.2021.1975473. eCollection 2021.


Accurate chromosome segregation depends on tight regulation of the protease separase, which cleaves the ring-shaped cohesin complex that entraps the two sister chromatids. We recently reported structures of human separase bound to its inhibitors securin or the cyclin-dependent kinase 1 (CDK1)-cyclin B1 (CCNB1)-cyclin-dependent kinases regulatory subunit 1 (CKS1) complex and discovered an array of molecular mechanisms that block cohesin-cleavage.

Keywords: Cell cycle; autoinhibition; caspase; cohesin; mitosis; oncogene; substrate occlusion.

Grant support

This work was supported by the Foundation Ernst et Lucie Schmidheiny; Novartis Stiftung für Medizinisch-Biologische Forschung [#19B074]; Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung [310030_185235].