Hubbard E J, Wu G, Kitajewski J, Greenwald I
Department of Biochemistry and Molecular Biophysics, Howard Hughes Medical Institute, New York, New York 10032, USA.
Genes Dev. 1997 Dec 1;11(23):3182-93. doi: 10.1101/gad.11.23.3182.
Mutations that influence lin-12 activity in Caenorhabditis elegans may identify conserved factors that regulate the activity of lin-12/Notch proteins. We describe genetic evidence indicating that sel-10 is a negative regulator of lin-12/Notch-mediated signaling in C. elegans. Sequence analysis shows that SEL-10 is a member of the CDC4 family of proteins and has a potential human ortholog. Coimmunoprecipitation data indicate that C. elegans SEL-10 complexes with LIN-12 and with murine Notch4. We propose that SEL-10 promotes the ubiquitin-mediated turnover of LIN-12/Notch proteins, and discuss potential roles for the regulation of lin-12/Notch activity by sel-10 in cell fate decisions and tumorigenesis.
影响秀丽隐杆线虫中lin-12活性的突变可能会鉴定出调控lin-12/Notch蛋白活性的保守因子。我们描述了遗传证据，表明sel-10是秀丽隐杆线虫中lin-12/Notch介导信号传导的负调节因子。序列分析表明，SEL-10是CDC4蛋白家族的成员，并且有一个潜在的人类直系同源物。免疫共沉淀数据表明，秀丽隐杆线虫的SEL-10与LIN-12以及小鼠Notch4形成复合物。我们提出SEL-10促进LIN-12/Notch蛋白的泛素介导的周转，并讨论sel-10对lin-12/Notch活性的调节在细胞命运决定和肿瘤发生中的潜在作用。
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