Kipreos E T, Gohel S P, Hedgecock E M
Department of Cellular Biology, The University of Georgia, Athens, Georgia 30602, USA.
Development. 2000 Dec;127(23):5071-82. doi: 10.1242/dev.127.23.5071.
In multicellular eukaryotes, a complex program of developmental signals regulates cell growth and division by controlling the synthesis, activation and degradation of G(1) cell cycle regulators. Here we describe the lin-23 gene of Caenorhabditis elegans, which is required to restrain cell proliferation in response to developmental cues. In lin-23 null mutants, all postembryonic blast cells undergo extra divisions, creating supernumerary cells that can differentiate and function normally. In contrast to the inability to regulate the extent of blast cell division in lin-23 mutants, the timing of initial cell cycle entry of blast cells is not affected. lin-23 encodes an F-box/WD-repeat protein that is orthologous to the Saccharomyces cerevisiae gene MET30, the Drosophila melanogaster gene slmb and the human gene betaTRCP, all of which function as components of SCF ubiquitin-ligase complexes. Loss of function of the Drosophila slmb gene causes the growth of ectopic appendages in a non-cell autonomous manner. In contrast, lin-23 functions cell autonomously to negatively regulate cell cycle progression, thereby allowing cell cycle exit in response to developmental signals.
在多细胞真核生物中，一个复杂的发育信号程序通过控制G(1)细胞周期调节因子的合成、激活和降解来调节细胞生长和分裂。在这里，我们描述了秀丽隐杆线虫的lin-23基因，它是响应发育线索抑制细胞增殖所必需的。在lin-23基因缺失的突变体中，所有胚胎后胚细胞都会进行额外的分裂，产生多余的细胞，这些细胞能够正常分化并发挥功能。与lin-23突变体中无法调节胚细胞分裂程度不同，胚细胞初始进入细胞周期的时间不受影响。lin-23编码一种F-box/ WD重复蛋白，它与酿酒酵母基因MET30、果蝇基因slmb和人类基因βTRCP是直系同源的，所有这些基因都作为SCF泛素连接酶复合物的组成部分发挥作用。果蝇slmb基因功能丧失会以非细胞自主的方式导致异位附肢的生长。相比之下，lin-23以细胞自主的方式发挥作用，负向调节细胞周期进程，从而允许细胞响应发育信号退出细胞周期。
