TEP1, the yeast homolog of the human tumor suppressor gene PTEN/MMAC1/TEP1, is linked to the phosphatidylinositol pathway and plays a role in the developmental process of sporulation
TEP1, the yeast homolog of the human tumor suppressor gene PTEN/MMAC1/TEP1, is linked to the phosphatidylinositol pathway and plays a role in the developmental process of sporulation
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DOI：
10.1073/pnas.97.23.12672
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发表时间：
2000-11-07
影响因子：
11.1
通讯作者：
Engebrecht, J
中科院分区：
文献类型：
--
作者：
Heymont, J;Berenfeld, L;Engebrecht, J
PTEN/MMAC 1/TEP 1（PTEN，在染色体10上缺失的磷酸酶; MMAC 1，在多种晚期癌症中突变; TEP 1，张力蛋白样磷酸酶）是主要的人类肿瘤抑制基因，其抑制活性对磷脂酰肌醇途径起作用。该基因的单一同源物TEP 1（YNL 128 w）存在于芽殖酵母酿酒酵母（Saccharomyces cerevisiae）中。TEP 1缺失的酵母菌株在单倍体中基本上没有表现出表型;然而，二倍体对磷脂酰肌醇-3-磷酸激酶抑制剂渥曼青霉素和锂离子表现出抗性。虽然癌症的发病率随着年龄的增长而增加，但无论是tep 1单倍体还是二倍体都没有改变寿命。TEP 1 RNA存在于整个细胞周期中，并且在减数分裂发育期间水平显著上调。虽然纯合tep 1突变体启动减数分裂程序，并形成孢子与野生型动力学，分析产生的孢子tep 1突变体表明一个特定的缺陷，在运输或沉积的二酪氨酸，酵母孢子壁的主要组成部分，表面。将在人类肿瘤中发现的常见的PTEN突变引入Tep 1 p中的类似位置产生基于体内活性的非功能性蛋白。这些研究暗示Tep 1 p在一个特定的发展贩运或沉积事件，并建议Tep 1 p，像它的哺乳动物对应物，冲击磷脂酰肌醇途径。
PTEN/MMAC1/TEP1 (PTEN, phosphatase deleted on chromosome ten; MMAC1, mutated in multiple advanced cancers; TEP1, tensin-like phosphatase) is a major human tumor suppressor gene whose suppressive activity operates on the phosphatidylinositol pathway. A single homologue of this gene, TEP1 (YNL128w) exists in the budding yeast Saccharomyces cerevisiae. Yeast strains deleted for TEP1 exhibit essentially no phenotype in haploids; however, diploids exhibit resistance to the phosphatidylinositol-3-phosphate kinase inhibitor wortmannin and to lithium ions. Although rates of cancer increase with age, neither tep1 haploids nor diploids have altered life spans. TEP1 RNA is present throughout the cell cycle, and levels are dramatically up-regulated during meiotic development. Although homozygous tep1 mutants initiate the meiotic program and form spores with wild-type kinetics, analysis of the spores produced in tep1 mutants indicates a specific defect in the trafficking or deposition of dityrosine, a major component of yeast spore walls, to the surface. introduction of a common PTEN mutation found in human tumors into the analogous position in Tep1p produces a nonfunctional protein based on in vivo activity. These studies implicate Tep1p in a specific developmental trafficking or deposition event and suggest that Tep1p, like its mammalian counterpart, impinges on the phosphatidylinositol pathway.