Cell cycle regulation by the pro-apoptotic gene Scotin.
Scotin is a pro-apoptotic mammalian gene, which is induced upon DNA damage or cellular stress in a p53-dependent manner. In this report, we have used Drosophila as a model system to obtain a preliminary insight into the molecular mechanism of Scotin function, which was further validated using the mammalian system. Targeted expression of Scotin in developing Drosophila induced apoptosis and developmental defects in wings and eyes. Co-expression of Scotin with the anti-apoptotic protein p35, while inhibited the apoptosis in both dividing and non-dividing cells, rescued adult wing or eye phenotypes only when Scotin was expressed in non-dividing cells. This suggests that mechanisms of Scotin-induced apoptosis in dividing and non-dividing cells may vary. Suppressor-enhancer screen using cell cycle regulators suggested that Scotin may mediate cell cycle arrest at both G(1)/S and G(2)/M phases. Overexpression of Scotin in mammalian cells resulted in mitotic arrest and subsequently apoptosis. Furthermore, a larger proportion of cells overexpressing Scotin showed sequestration of Cyclin B1 in the cytoplasm. These results suggest that one of the ways by which Scotin induces apoptosis is by causing cell cycle arrest.
Gupta
Rajesh Kumar
RK
Centre for Cellular and Molecular Biology, Hyderabad, India.
Tripathi
Rachana
R
Bhupana
Jagannatham Naidu
JN
Srinivas
Usha K
UK
Shashidhara
L S
LS
D000818:Animals; D030801:Animals, Genetically Modified; D017209:Apoptosis / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D019556:COS Cells; D002453:Cell Cycle / Q000235:genetics*; D002522:Chlorocebus aethiops; D019926:Cyclin B / Q000235:genetics; D056744:Cyclin B1; D019927:Cyclin E / Q000235:genetics / Q000502:physiology; D004330:Drosophila / Q000196:embryology / Q000235:genetics* / Q000254:growth & development; D004625:Embryo, Nonmammalian; D005123:Eye / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D018390:Gene Targeting; D005804:Genes, Lethal; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; C534701:Ccnb1 protein, rat; D019926:Cyclin B; D056744:Cyclin B1; D019927:Cyclin E; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins