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Separase, securin and Rad21 in neural cell growth
Author(s) -
Pemberton H.N.,
Franklyn J.A.,
Boelaert K.,
Chan S.Y.,
Kim D.S.,
Kim C.,
Cheng S.Y.,
Kilby M.D.,
McCabe C.J.
Publication year - 2007
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.21086
Subject(s) - separase , securin , microbiology and biotechnology , anaphase , mitosis , biology , chemistry , cell cycle , cell , genetics
Abstract The key mitotic regulator securin is expressed at low levels in fetal brain compared with adult, and modulates the proliferation of human embryonic neuronal N‐Tera2 (NT2) cells. We now examine the function and expression of securin's interacting partner separase, along with Rad21, the functional component of cohesin, which is cleaved by separase following interaction with securin. In contrast to securin, the cleaved forms of separase and Rad21 were highly expressed in human fetal cerebral cortex compared with adult. In a murine model of absent securin expression – the PTTG knock‐out mouse – separase and Rad21 were over‐expressed in multiple brain regions. In addition, cDNA array analysis of other key mitotic regulators additionally identified cyclin C and sestrin 2 to be induced in the brains of securin‐null mice compared with wild type. Further, Rad21 mRNA expression was highly correlated with that of securin, separase, cyclin C and sestrin 2 in fetal brains. In embryonic neuronal NT2 cells, siRNA repression of separase failed to significantly alter cell turnover, whereas repression of securin expression resulted in increased levels of the activated forms of Rad21 and separase, and promoted cell proliferation. Our data suggest that the co‐ordinated expression of separase, securin and Rad21 is fundamental for the developing brain. J. Cell. Physiol. 213: 45–53, 2007. © 2007 Wiley‐Liss, Inc.