Yeast UBL-UBA proteins have partially redundant functions in cell cycle control.
Yeast UBL-UBA proteins have partially redundant functions in cell cycle control.
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DOI：
10.1186/1747-1028-1-28
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发表时间：
2006-12-04
期刊：
影响因子：
2.3
通讯作者：
Clarke DJ
中科院分区：
文献类型：
--
作者：
Díaz-Martínez LA;Kang Y;Walters KJ;Clarke DJ
含有泛素样结构域(UBL)和泛素相关结构域(UBA)的蛋白质被认为可以将泛素化的底物穿梭到蛋白酶体上进行降解。在芽殖酵母中有三种含有UBL-UBA的蛋白质：Ddi1、Dsk2和RAD23，它们被证明在将泛素化的底物定向到蛋白酶体进行降解的过程中发挥着调节作用。据报道，这些蛋白质也参与了细胞周期相关的事件。我们测试了这三种蛋白质是否在细胞周期中起冗余作用。在这里，我们表明UBL-UBA蛋白对于细胞周期相关的角色是部分冗余的。RAD23与DDI1和DSK2是冗余的，但DDI1和DSK2之间不是冗余的，三重缺失显示了综合效应，提示RAD23在细胞周期调控中至少存在两个角色。RAD23Δddi1Δdsk2Δ三重缺失株在高温下的G2/M期和中期延迟，具有双纺锤体极体。三重缺失株的细胞周期进程只能被缺乏c-末端UBA结构域的RAD23等位基因部分挽救，这表明RAD23需要其c-末端UBA结构域才能发挥全部功能。除了与泛素和蛋白酶体结合的能力外，UBL-UBA蛋白还具有同源二聚的能力。RAD23和Dsk2二聚化需要它们的UBL和/或UBA结构域，而Ddi1二聚化不需要。在这里，我们证明了Ddi1同源二聚化是其细胞周期相关功能所必需的。这三种酵母菌的Ubl-Uba蛋白在有丝分裂过程中具有部分多余的功能。
Proteins containing ubiquitin-like (UBL) and ubiquitin associated (UBA) domains have been suggested to shuttle ubiquitinated substrates to the proteasome for degradation. There are three UBL-UBA containing proteins in budding yeast: Ddi1, Dsk2 and Rad23, which have been demonstrated to play regulatory roles in targeting ubiquitinated substrates to the proteasome for degradation. An involvement of these proteins in cell cycle related events has also been reported. We tested whether these three proteins act redundantly in the cell cycle. Here we show that the UBL-UBA proteins are partially redundant for cell cycle related roles. RAD23 is redundant with DDI1 and DSK2, but DDI1 and DSK2 are not redundant with each other and the triple deletion shows a synthetic effect, suggesting the existence of at least two roles for RAD23 in cell cycle control. The rad23Δddi1Δdsk2Δ triple deletion strain delays both in G2/M-phase and in mid-anaphase at high temperatures with duplicated spindle pole bodies. Cell cycle progression in the triple deletion strain can only be partially rescued by a rad23 allele lacking the c-terminal UBA domain, suggesting that RAD23 requires its c-terminal UBA domain for full function. In addition to their ability to bind ubiquitin and the proteasome, the UBL-UBA proteins also share the ability to homodimerize. Rad23 and Dsk2 dimerization requires their UBL and/or UBA domains whereas Ddi1 dimerization does not. Here we show that Ddi1 homodimerization is necessary for its cell cycle related functions. The three yeast UBL-UBA proteins have partially redundant roles required for progression through mitosis.
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影响因子：
5.3
作者：
Clarke, DJ;Mondesert, G;Reed, SI
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5.6
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4.1
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