Failure to farnesylate Rheb protein contributes to the enrichment of G0/G1 phase cells in the Schizosaccharomyces pombe farnesyltransferase mutant.
Failure to farnesylate Rheb protein contributes to the enrichment of G0/G1 phase cells in the Schizosaccharomyces pombe farnesyltransferase mutant.
复制标题
Rheb 蛋白法尼基化失败导致裂殖酵母法尼基转移酶突变体中 G0/G1 期细胞的富集。
DOI：
10.1046/j.1365-2958.2001.02599.x
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发表时间：
2001
影响因子：
3.6
通讯作者：
Tamanoi,F
中科院分区：
文献类型：
--
作者：
Yang,W;TabancayJr,AP;Urano,J;Tamanoi,F
蛋白质法尼基化对于许多生理过程是重要的，包括增殖和细胞形态。裂殖酵母pombemutant，cpp 1-，缺陷法尼基化，表现出不同的表型，包括形态变化和敏感性的精氨酸类似物，刀豆氨酸。在这项工作中，我们报告了一种新的表型，这种突变，富集G 0/G1期细胞。这种表型主要是由于Rheb G-蛋白不能法尼基化，因为正常的细胞周期进程可以通过表达可以绕过法尼基化的SpRheb突变形式（SpRheb‐CVIL）恢复到突变体。相比之下，SpRheb的法尼基化缺陷突变体（SpRheb‐SVIA）无法恢复pp 1突变体的正常细胞周期谱。SpRheb表达的抑制导致细胞在细胞周期的G 0/G1期积累。这种prheb破坏的生长停滞表型可以通过引入野生型prheb+来补充。这种补充依赖于法尼基化，因为法尼基化缺陷型SpRheb‐SVIA突变体不能补充prheb破坏。SpRheb的其它突变体E40 K和S20 N也不能补充这种破坏。此外，通过表达人Rheb而不是酵母Rheb可以获得有效的互补。我们的研究结果表明，蛋白质法尼基化是重要的细胞周期进程的S。pombecells和法尼基化的SpRheb在这个过程中是至关重要的。
Protein farnesylation is important for a number of physiological processes, including proliferation and cell morphology. TheSchizosaccharomyces pombemutant,cpp1–, defective in farnesylation, exhibits distinct phenotypes, including morphological changes and sensitivity to the arginine analogue, canavanine. In this work, we report a novel phenotype of this mutant, enrichment of G0/G1 phase cells. This phenotype results mainly from the inability to farnesylate the Rheb G‐protein, as normal cell cycle progression can be restored to the mutant by expressing a mutant form of SpRheb (SpRheb‐CVIL) that can bypass farnesylation. In contrast, a farnesylation‐defective mutant of SpRheb (SpRheb‐SVIA) is incapable of restoring the normal cell cycle profile to thecpp1–mutant. Inhibition of SpRheb expression leads to the accumulation of cells at the G0/G1 phase of the cell cycle. This growth arrest phenotype of thesprheb–disruption can be complemented by the introduction of wild‐typesprheb+.The complementation is dependent on farnesylation, as the farnesylation‐defective SpRheb‐SVIA mutant is incapable of complementing thesprheb–disruption. Other mutants of SpRheb, E40K and S20N, are also incapable of complementing thesprheb–disruption. Furthermore, efficient complementation can be obtained by the expression of human Rheb but notSaccharomyces cerevisiaeRheb. Our findings suggest that protein farnesylation is important for cell cycle progression ofS. pombecells and that farnesylated SpRheb is critical in this process.