Koerte A, Chong T, Li X, Wahane K, Cai M
Institute of Molecular and Cell Biology, National University of Singapore.
J Biol Chem. 1995 Sep 22;270(38):22556-64. doi: 10.1074/jbc.270.38.22556.
Mutations in the gene encoding p53 have been found to be the most common genetic alterations in human cancer, p53 is thought to exert its function of tumor suppression through inhibition of cell proliferation or induction of apoptosis in response to DNA damage. Although there have been no proteins homologous to p53 identified in lower eucaryotic organisms, it is known that overexpression of wild-type human p53 can inhibit cell growth of Schizosaccharomyces pombe and Saccharomyces cerevisiae (Bischoff et al., 1992; Nigro et al., 1992), suggesting that certain aspects of p53 function may manifest or exist in yeast. In an attempt to identify the p53-like proteins in the yeast S. cerevisiae, we isolated a mutant that requires wild-type p53 for its viability. The mutant, rft1-1, is defective in cell cycle progression and arrests before mitosis when p53 protein is depleted. Genetic and biochemical studies show that p53 suppresses the rft1-1 mutation by forming a protein-protein complex with the Rft1 protein.
编码p53的基因发生突变是人类癌症中最常见的基因改变,p53被认为是通过抑制细胞增殖或在DNA损伤时诱导细胞凋亡来发挥其肿瘤抑制功能的。虽然在低等真核生物中尚未鉴定出与p53同源的蛋白质,但已知野生型人p53的过表达可抑制粟酒裂殖酵母和酿酒酵母的细胞生长(Bischoff等人,1992年;Nigro等人,1992年),这表明p53功能的某些方面可能在酵母中表现出来或存在。为了鉴定酿酒酵母中的p53样蛋白,我们分离出了一个其存活需要野生型p53的突变体。该突变体rft1-1在细胞周期进程中存在缺陷,当p53蛋白耗尽时,在有丝分裂前停滞。遗传和生化研究表明,p53通过与Rft1蛋白形成蛋白质-蛋白质复合物来抑制rft1-1突变。