fzr-1 and lin-35/Rb function redundantly to control cell proliferation in C-elegans as revealed by a nonbiased synthetic screen

被引:117
作者
Fay, DS
Keenan, S
Han, M
机构
[1] Univ Colorado, Howard Hughes Med Inst, Boulder, CO 80309 USA
[2] Univ Colorado, Dept Mol Cellular & Dev Biol, Boulder, CO 80309 USA
关键词
lin-35; retinoblastoma; fizzy related; fzr-1; C; elegans; hyperproliferation; synthetic screen;
D O I
10.1101/gad.952302
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
We report here a synthetic-lethal screen in Caenorhabditis elegans that overcomes a number of obstacles associated with the analysis of functionally redundant genes. Using this approach, we have identified mutations that synthetically interact with lin-35/Rb, a SynMuv gene and the sole member of the Rb/pocket protein family in C. elegans. Unlike the original SynMuv screens, our approach is completely nonbiased and can theoretically be applied to any situation in which a mutation fails to produce a detectable phenotype. From this screen we have identified fzr-1, a gene that synthetically interacts with lin-35 to produce global defects in cell proliferation control. fzr-1 encodes the C. elegans homolog of Cdh1/Hct1/FZR, a gene product shown in other systems to regulate the APC cyclosome. We have also uncovered genetic interactions between fzr-1 and a subset of class B SynMuv genes, and between lin-35 and the putative SCF regulator lin-23. We propose that lin-35, fzr-1, and lin-23 function redundantly to control cell cycle progression through the regulation of cyclin levels.
引用
收藏
页码:503 / 517
页数:15
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