Yamashita Y M, Nakaseko Y, Samejima I, Kumada K, Yamada H, Michaelson D, Yanagida M
Department of Biophysics, Graduate School of Science, Kyoto University, Japan.
Nature. 1996 Nov 21;384(6606):276-9. doi: 10.1038/384276a0.
The 20S cyclosome complex (also known as the anaphase-promoting complex) has ubiquitin ligase activity and is required for mitotic cyclin destruction and sister chromatid separation. The formation and activation of the 20S cyclosome complex is regulated by an unknown mechanism. Here we show that Cut4 (ref. 6) is an essential component of the cyclosome in fission yeast. Cut4 shares sequence similarity with BimE, a protein that regulates mitosis in Aspergillus nidulans. Mutations in cut4 result in hypersensitivity to cyclic AMP and to stress-inducing heavy metals, inhibition of the onset of anaphase, disruption of the 20S complex, and inhibition of mitotic cyclin ubiquitination. These phenotypes are fully suppressed by cAMP phosphodiesterase and the protein kinase A (PKA) regulatory subunit and weakly suppressed by Sti1 (an activator of the Hsp70 and Hsp90 chaperones). Suppression correlates with the amount of 20S complex, indicating that cyclosome formation and activation is inhibited by the cAMP/PKA pathway.
20S 环体复合物（也称为后期促进复合物）具有泛素连接酶活性，是有丝分裂周期蛋白降解和姐妹染色单体分离所必需的。20S 环体复合物的形成和激活受未知机制调控。在此我们表明，Cut4（参考文献 6）是裂殖酵母中环体的一个必需组分。Cut4 与 BimE 具有序列相似性，BimE 是一种调节构巢曲霉有丝分裂的蛋白质。cut4 中的突变导致对环磷酸腺苷（cAMP）和应激诱导重金属的超敏反应、后期起始的抑制、20S 复合物的破坏以及有丝分裂周期蛋白泛素化的抑制。这些表型被 cAMP 磷酸二酯酶和蛋白激酶 A（PKA）调节亚基完全抑制，被 Sti1（Hsp70 和 Hsp90 伴侣蛋白的激活剂）微弱抑制。抑制作用与 20S 复合物的量相关，表明环体的形成和激活被 cAMP/PKA 途径抑制。
