Intertwined Functions of Separase and Caspase in Cell Division and Programmed Cell Death.

TitleIntertwined Functions of Separase and Caspase in Cell Division and Programmed Cell Death.
Publication TypeJournal Article
Year of Publication2020
AuthorsJeong PYoung, Kumar A, Joshi PM, Rothman JH
JournalSci Rep
Date Published2020 04 09
KeywordsAnimals, Apoptosis, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Caspases, Cell Division, Female, Male, Separase

Timely sister chromatid separation, promoted by separase, is essential for faithful chromosome segregation. Separase is a member of the CD clan of cysteine proteases, which also includes the pro-apoptotic enzymes known as caspases. We report a role for the C. elegans separase SEP-1, primarily known for its essential activity in cell division and cortical granule exocytosis, in developmentally programmed cell death when the predominant pro-apoptotic caspase CED-3 is compromised. Loss of SEP-1 results in extra surviving cells in a weak ced-3(-) mutant, and suppresses the embryonic lethality of a mutant defective for the apoptotic suppressor ced-9/Bcl-2 implicating SEP-1 in execution of apoptosis. We also report apparent non-apoptotic roles for CED-3 in promoting germ cell proliferation, meiotic chromosome disjunction, egg shell formation, and the normal rate of embryonic development. Moreover, loss of the soma-specific (CSP-3) and germline-specific (CSP-2) caspase inhibitors result in CED-3-dependent suppression of embryonic lethality and meiotic chromosome non-disjunction respectively, when separase function is compromised. Thus, while caspases and separases have evolved different substrate specificities associated with their specialized functions in apoptosis and cell division respectively, they appear to have retained the residual ability to participate in both processes, supporting the view that co-option of components in cell division may have led to the innovation of programmed cell suicide early in metazoan evolution.

Alternate JournalSci Rep
PubMed ID32273538
PubMed Central IDPMC7145830
Grant ListR01 HD081266 / HD / NICHD NIH HHS / United States
R01 HD082347 / HD / NICHD NIH HHS / United States