Separase, securin and Rad21 in neural cell growth

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.

Effects of a Tricaprylin Emulsion on Anti-glomerular Basement Membrane Glomerulonephritis in Rats: <i>In Vivo</i> and <i>in Silico</i> Studies

“…[25][26][27] These results suggested that the expression of genes in the GO terms related to the cell cycle were commonly affected in the different models of nephritis, especially in our anti-GBM GN rat model, whereas no significant changes in expression could be detected in the anti-GBM GN rat with administration of the tricaprylin emulsion or emodin compared with the control rats. Furthermore, in cluster c, d, and e, the GO terms were overrepresented in "GBM vs. C" and "E vs. C," but not in "TC vs. C" (cluster c, d, e in Fig.…”

Sestrins Link Tumor Suppressors with the AMPK-TOR Signaling Network

“…Impact inflammation in Sesn2 expression might be mediated by NO-production, and accordingly NO is the Sesn2 activator [128]. Sesn2 is also activated in the brain of Securin-deficient mice [129]. Securin is a protein, which in complex with Separase, regulates chromosomal separation and metaphase-anaphase transition [129].…”

“…Sesn2 is also activated in the brain of Securin-deficient mice [129]. Securin is a protein, which in complex with Separase, regulates chromosomal separation and metaphase-anaphase transition [129]. Securin deficiency causes genomic instability and might regulate Sesn2 via p53 activation.…”

WOMEN IN CANCER PROFILE: From bedside to bench and back: my journey in thyroid disease

“…Detailed investigations determined that both PTTG and PBF repress the expression, localisation and function of the sodium iodide symporter (NIS), thereby crucially affecting treatment of thyroid tumours with radioiodine (Boelaert et al 2007, Smith et al 2009). PTTG was also identified as human securin, an important protein in normal mitosis, and additional investigations performed during my PhD studies elucidated a potential role for PTTG in human foetal brain development (Boelaert et al 2003b, Pemberton et al 2007).…”

“…Detailed investigations determined that both PTTG and PBF repress the expression, localisation and function of the sodium iodide symporter (NIS), thereby crucially affecting treatment of thyroid tumours with radioiodine (Boelaert et al 2007, Smith et al 2009). PTTG was also identified as human securin, an important protein in normal mitosis, and additional investigations performed during my PhD studies elucidated a potential role for PTTG in human foetal brain development (Boelaert et al 2003b, Pemberton et al 2007). Overall, the findings obtained during my PhD studies have laid the foundations for a large collaborative programme of laboratory research investigating the pathogenesis of endocrine neoplasia and more recently the exploration of novel approaches into the re-engineering of radio-iodine for refractory thyroid cancer.…”