Kaul S C, Duncan E L, Englezou A, Takano S, Reddel R R, Mitsui Y, Wadhwa R
National Institute of Bioscience and Human Technology, AIST, Tsukuba, Ibaraki, Japan.
Oncogene. 1998 Aug 20;17(7):907-11. doi: 10.1038/sj.onc.1202017.
The murine mortalin genes, mot-1 and mot-2, are members of the hsp70 family of proteins and differ from each other by only two amino acid residues. Mot-1 is expressed in normal cells and has pancytosolic cellular distribution whereas mot-2 is found in the perinuclear region of immortal cells. We report here that a high level of expression of mot-2 protein resulted in malignant transformation of cells as analysed by anchorage independent growth and nude mice assays. A high level of protein expression is attributed to the 900 bp 3' untranslated region of the cDNA which does not have any transforming activity per se. Mortalin cDNA clones isolated from human transformed cells were also found to have transforming activity in similar assays and a high level of expression was apparent in some of the human immortalized cells that showed non-pancytosolic mortalin immunofluorescence. Taken together, the data suggest that nonpancytosolic mortalin may have a role in tumorigenesis.
小鼠mortalin基因mot-1和mot-2是热休克蛋白70(hsp70)家族蛋白的成员,彼此仅相差两个氨基酸残基。Mot-1在正常细胞中表达,在细胞内呈全胞质分布,而mot-2则存在于永生化细胞的核周区域。我们在此报告,通过锚定非依赖性生长和裸鼠试验分析,mot-2蛋白的高表达导致细胞发生恶性转化。蛋白的高表达归因于cDNA的900 bp 3'非翻译区,其本身没有任何转化活性。从人转化细胞中分离出的mortalin cDNA克隆在类似试验中也具有转化活性,并且在一些显示非全胞质mortalin免疫荧光的人永生化细胞中明显有高表达。综上所述,数据表明非全胞质mortalin可能在肿瘤发生中起作用。