β2 subunit propeptides influence cooperative proteasome assembly
β2 subunit propeptides influence cooperative proteasome assembly
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DOI：
10.1074/jbc.m209292200
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发表时间：
2003-02-21
影响因子：
4.8
通讯作者：
Griffin, TA
中科院分区：
文献类型：
--
作者：
De, M;Jayarapu, K;Griffin, TA
脊椎动物的蛋白酶体在结构上是异质的，由“组成型”（或“标准”）蛋白酶体和“免疫蛋白酶体”组成。组成性蛋白酶体含有三个普遍表达的催化亚基，Delta（β 1），Z（β 2）和X（β 5），而免疫蛋白酶体含有三个干扰素-γ诱导的催化亚基，LMP 2（β 1 i），MECL（β 2 i）和LMP 7（β 5 i）。我们最近已经证明，蛋白酶体组装偏向于促进免疫蛋白酶体的同质性时，两种类型的催化亚基在同一个细胞中表达。这种协同组装部分是由于LMP 7（β 5 i）和X（β 5）前肽之间的差异。在目前的研究中，我们证明了MECL（β 2 i）和Z（β 2）前肽之间的差异也影响协同组装。具体地，用Z的前肽替换MECL前肽使得MECL能够掺入到另外的组成型（Delta（+）/X+）蛋白酶体中，并促进X掺入到另外的免疫蛋白酶体（MECL+/LMP 2（+））中。我们还表明，使用MECL-/-小鼠，LMP 2掺入不需要MECL，与以前的建议，他们的掺入是相互依赖的。这些结果使我们能够完善我们的合作蛋白酶体组装模型，通过确定哪些组合的诱导型和组成型亚基比其他人更受欢迎，我们提出了一个机制，如何前肽介导的合作组装。
Vertebrate proteasomes are structurally heterogeneous, consisting of both "constitutive" (or "standard") proteasomes and "immunoproteasomes." Constitutive proteasomes contain three ubiquitously expressed catalytic subunits, Delta (beta1), Z (beta2), and X (beta5), whereas immunoproteasomes contain three interferon-gamma-inducible catalytic subunits, LMP2 (beta1i), MECL (beta2i), and LMP7 (beta5i). We recently have demonstrated that proteasome assembly is biased to promote immunoproteasome homogeneity when both types of catalytic subunits are expressed in the same cell. This cooperative assembly is due in part to differences between the LMP7 (beta5i) and X (beta5) propeptides. In the current study we demonstrate that differences between the MECL (beta2i) and Z (beta2) propeptides also influence cooperative assembly. Specifically, replacing the MECL propeptide with that of Z enables MECL incorporation into otherwise constitutive (Delta(+)/X+) proteasomes and facilitates X incorporation into otherwise immunoproteasomes (MECL+/LMP2(+)). We also show, using MECL-/- mice, that LMP2 incorporation does not require MECL, in contrast with previous suggestions that their incorporation is mutually codependent. These results enable us to refine our model for cooperative proteasome assembly by determining which combinations of inducible and constitutive subunits are favored over others, and we propose a mechanism for how propeptides mediate cooperative assembly.