Separase, securin and Rad21 in neural cell growth.
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.
Pemberton
H N
HN
Divisions of Medical Sciences, University of Birmingham, Queen Elizabeth Hospital, Birmingham, B15 2TH, UK.
Franklyn
J A
JA
Boelaert
K
K
Chan
S Y
SY
Kim
D S
DS
Kim
C
C
Cheng
S Y
SY
Kilby
M D
MD
McCabe
C J
CJ
D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D049109:Cell Proliferation; D056745:Cyclin C; D016213:Cyclins / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D004268:DNA-Binding Proteins; D010450:Endopeptidases / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D064249:Securin; D064247:Separase; D000084622:Sestrins
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D056745:Cyclin C; D016213:Cyclins; D017931:DNA Primers; D004268:DNA-Binding Proteins; D010450:Endopeptidases; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D064249:Securin; D064247:Separase; C503674:CCNC protein, human; C429022:RAD21 protein, human; C465862:Rad21 protein, mouse; C465398:SESN2 protein, human; D000084622:Sestrins; C578002:pituitary tumor-transforming protein 1, human; C577987:ESPL1 protein, human