Disease relevance of Espl1

• Collectively, these experimental data suggest that SSE could be not harmful for women with a history of or at high risk for breast cancer, at least for short treatment periods; however, further studies are needed to thoroughly characterize the activity profile of the extract in this specific setting of patients [1].
• In this investigation, kallikrein-like prorenin converting enzyme (PRCE C) (mK9) is isolated from genetically inbred high blood pressure (BPH) and their normal counterparts (BPN) mice, and its protein levels are quantitated [2].
• Mice and rabbits were immunised with sodium salicylate extracts (SSE) prepared from each of 12 serotypes of Pasteurella haemolytica, and the antisera to each were used in cross-indirect haemagglutination (IHA) tests and cross-enzyme-linked immunosorbent assays (ELISA) to study antigenic relationships between the serotypes [3].

High impact information on Espl1

• Although our work shows that separase is required for sister chromatid separation in higher eukaryotes, in addition, it also indicates that the regulatory proteins have diverged to a surprising degree, particularly in Drosophila [4].
• However, our genetic analyses show that SSE is essential and required for sister chromatid separation during mitosis [4].
• Securin binds and inhibits separase, a conserved cysteine endoprotease [4].
• We have created conditional knockout alleles of the mouse Separase and Securin genes [5].
• In embryonic fibroblasts, Separase depletion blocks sister chromatid separation but does not prevent other aspects of mitosis, cytokinesis, or chromosome replication [5].

Chemical compound and disease context of Espl1

• The present study was designed to investigate the effects of a phytoestrogens-containing soy extract (SOYSELECT, SSE) on the growth of estrogen-dependent (MCF-7) and estrogen-unresponsive (MDA-MB-231) human breast cancer xenografts in athymic mice [1].

Biological context of Espl1

• We therefore investigated if Separase activity is required for correct chromosome segregation in meiosis I in mouse oocytes [6].
• In yeast and worms, the segregation of homologous chromosomes in meiosis I depends on the APC/C and Separase activity [6].
• After securin degradation, Separase cleaves the cohesins and triggers chromatid separation, a prerequisite for anaphase [6].
• One candidate mechanism is the inhibitory phosphorylation of separase [7].
• Separase: a universal trigger for sister chromatid disjunction but not chromosome cycle progression [5].

Anatomical context of Espl1

• Yet, it is unclear if Separase is required for the first meiotic division in vertebrates because APC/C activity is thought to be dispensable in frog oocytes [6].
• We generated a nonphosphorylable point mutant (S1121A) separase allele in securin-/- mouse embryonic stem cells [7].
• Thus, fibroblasts lacking Separase become highly polyploid [5].
• Separase depletion in bone marrow causes aplasia and the presumed death of hematopoietic cells other than erythrocytes [5].
• Hepatocytes stimulated to proliferate in vivo by hepatectomy also become unusually large and polyploid in the absence of Separase but are able to regenerate functional livers [5].

Associations of Espl1 with chemical compounds

• Separase is a cysteine protease that participates in separation of sister chromatids during mitosis [8].
• Results obtained provided evidence that MCF-7 tumors did not grow over the treatment period (5 weeks) in ovariectomized females receiving 50 or 100 mg/kg/day SSE (oral route); administration of SSE also did not affect the estradiol-sustained growth of MCF-7 tumors in mice [1].
• The expression of other genes involved in tumor progression and angiogenesis, such as Thrombospondin 1, Transforming Growth Factor beta2 and Kallikrein 6 was also evaluated in tumor samples, results showing a decrease in mRNA expression upon SSE treatment [1].
• This antigen was extracted from the SSE with hot phenol/water and analysed by gas chromatography [9].

Enzymatic interactions of Espl1

• Separase is an evolutionarily conserved protease that is essential for chromosome segregation and cleaves cohesin Scc1/Rad21, which joins the sister chromatids together [10].

Other interactions of Espl1

• Although securin/separase/cohesion pathway was reported to regulate chromosome segregation during meiotic metaphase-to-anaphase transition, little biochemical evidence was provided [11].

Analytical, diagnostic and therapeutic context of Espl1

• The described separase-specific antibodies were suitable for detection of endogenous separase in crude extracts, immunoprecipitation, and immunofluorescent cell staining experiments [8].
• Similarly, no effects on tumor growth were observed in SSE-treated mice bearing MDA-MB-231 xenografts [1].
• In situ hybridization histochemistry results localized PRCE C (mK9) in the striated duct cells of submandibular gland [2].

References