A multimeric assembly factor controls the formation of alternative 20S proteasomes
A multimeric assembly factor controls the formation of alternative 20S proteasomes
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DOI：
10.1038/nsmb.1389
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发表时间：
2008-03-01
影响因子：
16.8
通讯作者：
Hochstrasser, Mark
中科院分区：
文献类型：
--
作者：
Kusmierczyk, Andrew R.;Kunjappu, Mary J.;Hochstrasser, Mark
蛋白酶体是真核细胞的中央调节蛋白酶。异七聚体 α 亚基和 β 亚基环堆叠形成 20S 蛋白酶体，与 19S 调节颗粒 (RP) 结合。在这里，我们展示了两种酵母蛋白 Pba3 和 Pba4，形成了先前未鉴定的 20S 蛋白酶体组装伴侣。 Pba3-Pba4 在遗传和物理上与特定的蛋白酶体 α 亚基相互作用，Pba3-Pba4 的丢失会导致细胞蛋白酶体的减少和重塑。值得注意的是，突变细胞会积累蛋白酶体，其中 α 4 亚基的第二个副本取代了 α 3。20S 蛋白酶体组装缺陷也与 RP 组装的改变有关。这一意想不到的结果表明 20S 蛋白酶体可以在体内充当 RP 组装因子。我们的数据表明，Pba3-Pba4 协调特定类型蛋白酶体的形成，这是控制替代蛋白酶体复合物组装的反式作用因子的第一个例子。
The proteasome is the central regulatory protease of eukaryotic cells. Heteroheptameric alpha-subunit and beta-subunit rings stack to form the 20S proteasome, which associates with a 19S regulatory particle (RP). Here we show that two yeast proteins, Pba3 and Pba4, form a previously unidentified 20S proteasome-assembly chaperone. Pba3-Pba4 interacts genetically and physically with specific proteasomal alpha subunits, and loss of Pba3-Pba4 causes both a reduction and a remodeling of cellular proteasomes. Notably, mutant cells accumulate proteasomes in which a second copy of the alpha 4 subunit replaces alpha 3. 20S proteasome-assembly defects also are associated with altered RP assembly; this unexpected result suggests that the 20S proteasome can function as an RP-assembly factor in vivo. Our data demonstrate that Pba3-Pba4 orchestrates formation of a specific type of proteasome, the first example of a trans-acting factor that controls assembly of alternative proteasomal complexes.