Securin is not required for cellular viability, but is required for normal growth of mouse embryonic fibroblasts.
Sister chromatid separation depends on the release of cohesion by the activity of Esp1, a member of the caspase family [1, 2]. In budding yeast, Esp1p is kept inactive by its association with Pds1p, until the onset of anaphase, when Pds1p is ubiquitinated by the APC/Cdc20 complex [3--5] and subsequently degraded by the 26S proteasome. Pds1 is not an essential gene in budding yeast, but is required for cell cycle arrest prior to anaphase in response to the disruption of spindle structures [6, 7]. Thus, Pds1 mutant yeast cells display precocious sister chromatid separation in the presence of nocodazole [6]. Mammalian orthologs of yeast Esp1 and Pds1, separin and securin, have been identified [8], and, as anticipated, a nondegradable mutant form of securin inhibits sister separation when added to mitotic Xenopus egg extracts [8]. Securin was also independently identified as PTTG (pituitary tumor transforming gene), a gene overexpressed in pituitary tumors [9]. The relationship between its overexpression in tumors and its control of sister chromatid cohesion remains ill defined. To explore securin function in mammals, we took a targeted gene disruption approach in mice. Here, we report that securin is neither essential for cell viability nor required for spindle checkpoint function, and mice lacking securin are viable and apparently normal, but mouse embryonic fibroblasts lacking securin grow abnormally in culture.
Mei
J
J
Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX 77030, USA.
Huang
X
X
Zhang
P
P
D000818:Animals; D001483:Base Sequence; D018797:Cell Cycle Proteins / Q000502:physiology*; D002455:Cell Division / Q000502:physiology*; D017931:DNA Primers; D003703:Demecolcine / Q000494:pharmacology; D004622:Embryo, Mammalian / Q000166:cytology* / Q000187:drug effects; D004625:Embryo, Nonmammalian; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D051379:Mice; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects; D014981:Xenopus
D018797:Cell Cycle Proteins; D017931:DNA Primers; D003703:Demecolcine