Stirling Peter C, Srayko Martin, Takhar Karam S, Pozniakovsky Andrei, Hyman Anthony A, Leroux Michel R
Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia, Canada V5A 1S6.
Mol Biol Cell. 2007 Jun;18(6):2336-45. doi: 10.1091/mbc.e07-01-0069. Epub 2007 Apr 11.
The Chaperonin Containing Tcp1 (CCT) maintains cellular protein folding homeostasis in the eukaryotic cytosol by assisting the biogenesis of many proteins, including actins, tubulins, and regulators of the cell cycle. Here, we demonstrate that the essential and conserved eukaryotic phosducin-like protein 2 (PhLP2/PLP2) physically interacts with CCT and modulates its folding activity. Consistent with this functional interaction, temperature-sensitive alleles of Saccharomyces cerevisiae PLP2 exhibit cytoskeletal and cell cycle defects. We uncovered several high-copy suppressors of the plp2 alleles, all of which are associated with G1/S cell cycle progression but which do not appreciably affect cytoskeletal protein function or fully rescue the growth defects. Our data support a model in which Plp2p modulates the biogenesis of several CCT substrates relating to cell cycle and cytoskeletal function, which together contribute to the essential function of PLP2.
含TCP1的伴侣蛋白（CCT）通过协助许多蛋白质的生物合成，包括肌动蛋白、微管蛋白和细胞周期调节因子，维持真核细胞质中的细胞蛋白质折叠稳态。在此，我们证明了必需且保守的真核类磷光蛋白2（PhLP2/PLP2）与CCT发生物理相互作用并调节其折叠活性。与这种功能相互作用一致，酿酒酵母PLP2的温度敏感等位基因表现出细胞骨架和细胞周期缺陷。我们发现了几个plp2等位基因的高拷贝抑制子，它们都与G1/S细胞周期进程相关，但对细胞骨架蛋白功能没有明显影响，也不能完全挽救生长缺陷。我们的数据支持一种模型，即Plp2p调节与细胞周期和细胞骨架功能相关的几种CCT底物的生物合成，这些底物共同促成了PLP2的基本功能。
