Pukatzki S, Tordilla N, Franke J, Kessin R H
Department of Anatomy and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
J Biol Chem. 1998 Sep 11;273(37):24131-8. doi: 10.1074/jbc.273.37.24131.
A novel component of the ubiquitination system, called NOSA, is essential for cellular differentiation in Dictyostelium discoideum. Disruption of nosA does not affect the growth rate but causes an arrest in development after the cells have aggregated. nosA contains seven exons and codes for a developmentally regulated 3.5-kb mRNA. The 125-kDa NOSA protein is present in the cytosol at constant levels during growth and development. The C-terminal region of NOSA has homology with ubiquitin fusion degradation protein-2 (UFD2) of Saccharomyces cerevisiae and putative homologs in Caenorhabditis elegans and humans. UFD2 is involved in the ubiquitin-mediated degradation of model substrates in which ubiquitin forms part of the translation product, but ufd2 mutants have no detected phenotype. In accord with the homology to UFD2, we found differences in the ubiquitination patterns between nosA mutants and their parental cell line. While general in vivo and in vitro ubiquitination is minimally affected, ubiquitination of individual proteins is altered throughout growth and development in nosA mutants. These findings suggest that events involving ubiquitination are critical for progression through the aggregate stage of the Dictyostelium life cycle.
泛素化系统的一个名为NOSA的新成分，对盘基网柄菌的细胞分化至关重要。nosA的破坏不影响生长速率，但会导致细胞聚集后发育停滞。nosA包含七个外显子，编码一种受发育调控的3.5kb mRNA。125kDa的NOSA蛋白在生长和发育过程中以恒定水平存在于细胞质中。NOSA的C末端区域与酿酒酵母的泛素融合降解蛋白2（UFD2）以及秀丽隐杆线虫和人类中的推定同源物具有同源性。UFD2参与泛素介导的模型底物降解，其中泛素是翻译产物的一部分，但ufd2突变体未检测到表型。与与UFD2的同源性一致，我们发现nosA突变体与其亲本细胞系之间的泛素化模式存在差异。虽然一般的体内和体外泛素化受到的影响最小，但在nosA突变体的整个生长和发育过程中，个别蛋白质的泛素化发生了改变。这些发现表明，涉及泛素化的事件对于盘基网柄菌生命周期中聚集阶段的进展至关重要。
