A longevity protein, Lag2, interacts with SCF complex and regulates SCF function
A longevity protein, Lag2, interacts with SCF complex and regulates SCF function
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DOI：
10.1038/emboj.2009.268
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发表时间：
2009-11-04
期刊：
影响因子：
11.4
通讯作者：
Kamura, Takumi
中科院分区：
文献类型：
--
作者：
Liu, Yuan;Mimura, Satoru;Kamura, Takumi
SCF型E3-泛素连接酶通过泛素-蛋白酶体途径控制许多细胞过程。然而，SCF功能的调节在很大程度上仍然是未知的。在这里，我们报告了一种新的SCF复合物相互作用蛋白，Lag 2，在酿酒酵母。Lag 2在生理条件下与SCF复合物相互作用。Lag 2通过阻断Cdc 34与SCF复合物的结合来负调控SCF E3连接酶的泛素化活性。过表达的Lag 2增加unrubylated Cdc 53，而删除lag 2，连同dcn 1和jab 1的缺失，在Rub 1修饰的Cdc 53的积累的结果。体外红宝石化实验表明，Lag 2抑制Rub 1与Cdc 53的结合，与Dcn 1竞争，表明Lag 2下调Cdc 53的红宝石化，而不是促进去红宝石化。此外，Dcn 1在体内阻碍了Lag 2与Cdc 53的结合。最后，lag 2的缺失与dcn 1或rub 1的缺失相结合抑制了酵母细胞的生长。因此，这些观察结果表明，Lag 2通过控制其泛素连接酶活性和红宝石化循环在调节SCF复合物中具有重要功能。EMBO期刊（2009）28，3366-3377。doi：10.1038/emboj.2009.268;在线发布于2009年9月17日
SCF-type E3-ubiquitin ligases control numerous cellular processes through the ubiquitin-proteasome pathway. However, the regulation of SCF function remains largely uncharacterized. Here, we report a novel SCF complex-interacting protein, Lag2, in Saccharomyces cerevisiae. Lag2 interacts with the SCF complex under physiological conditions. Lag2 negatively controls the ubiquitylation activities of SCF E3 ligase by interrupting the association of Cdc34 to SCF complex. Overexpression of Lag2 increases unrubylated Cdc53, whereas deletion of lag2, together with the deletions of dcn1 and jab1, results in the accumulation of Rub1-modified Cdc53. In vitro rubylation assays show that Lag2 inhibits the conjugation of Rub1 to Cdc53 in competition with Dcn1, which suggest that Lag2 down-regulates the rubylation of Cdc53 rather than promoting derubylation. Furthermore, Dcn1 hinders the association of Lag2 to Cdc53 in vivo. Finally, the deletion of lag2 combined with the deletion of either dcn1 or rub1 suppresses the growth of yeast cells. These observations thus indicate that Lag2 has a significant function in regulating the SCF complex by controlling its ubiquitin ligase activities and its rubylation cycle. The EMBO Journal (2009) 28, 3366-3377. doi: 10.1038/emboj.2009.268; Published online 17 September 2009