Proteaphagy is specifically regulated and requires factors dispensable for general autophagy.
Proteaphagy is specifically regulated and requires factors dispensable for general autophagy.
复制标题
DOI：
10.1016/j.jbc.2021.101494
复制
发表时间：
2022-01
期刊：
影响因子：
--
通讯作者：
Roelofs J
中科院分区：
文献类型：
--
作者：
Waite KA;Burris A;Vontz G;Lang A;Roelofs J
改变生理条件可以增加真核细胞对蛋白质降解能力的需求。泛素-蛋白酶体系统和自噬都有助于蛋白质降解。然而，这些过程可以根据生理条件进行不同的调节。引人注目的是，蛋白酶体本身可以成为自噬的底物。控制蛋白酶体自噬的信号和分子机制只被部分理解。在这里，我们使用免疫印迹，天然凝胶分析和荧光显微镜，以了解调节蛋白吞噬反应的遗传和小分子诱导的扰动。我们的数据表明，用雷帕霉素化学抑制主营养素传感器TORC 1（抑制其诱导一般自噬）诱导双相反应，其中蛋白酶体水平在自噬依赖性减少后上调。令人惊讶的是，导致抑制的TORC 1的几种条件，如咖啡因处理或氮饥饿，仅诱导蛋白吞噬（即，没有任何蛋白酶体上调），这表明在不同生理条件下蛋白吞噬上游信号的会聚。事实上，我们发现激活一般自噬的几种条件并不诱导蛋白自噬，从而进一步将蛋白自噬与一般自噬区分开来。与此一致，我们表明，Atg11，一种选择性自噬受体，以及MAP激酶Mpk 1，Mkk 1和Mkk 2都发挥作用的蛋白酶体的自噬，虽然他们是一般的自噬。两者合计，我们的数据提供了新的见解蛋白吞噬的分子调控，通过证明蛋白酶体复合物的降解是特别调节不同的自噬诱导条件下。
Changing physiological conditions can increase the need for protein degradative capacity in eukaryotic cells. Both the ubiquitin-proteasome system and autophagy contribute to protein degradation. However, these processes can be differently regulated depending on the physiological conditions. Strikingly, proteasomes themselves can be a substrate for autophagy. The signals and molecular mechanisms that govern proteasome autophagy (proteaphagy) are only partly understood. Here, we used immunoblots, native gel analyses, and fluorescent microscopy to understand the regulation of proteaphagy in response to genetic and small molecule-induced perturbations. Our data indicate that chemical inhibition of the master nutrient sensor TORC1 (inhibition of which induces general autophagy) with rapamycin induces a bi-phasic response where proteasome levels are upregulated after an autophagy-dependent reduction. Surprisingly, several conditions that result in inhibited TORC1, such as caffeinine treatment or nitrogen starvation, only induced proteaphagy (i.e., without any proteasome upregulation), suggesting a convergence of signals upstream of proteaphagy under different physiological conditions. Indeed, we found that several conditions that activated general autophagy did not induce proteaphagy, further distinguishing proteaphagy from general autophagy. Consistent with this, we show that Atg11, a selective autophagy receptor, as well as the MAP kinases Mpk1, Mkk1, and Mkk2 all play a role in autophagy of proteasomes, although they are dispensable for general autophagy. Taken together, our data provide new insights into the molecular regulation of proteaphagy by demonstrating that degradation of proteasome complexes is specifically regulated under different autophagy-inducing conditions.
登录
查看更多内容
影响因子：
7.8
作者：
Baba, M;Osumi, M;Scott, SV;Klionsky, DJ;Ohsumi, Y
通讯作者：
Ohsumi, Y
DOI：
10.1073/pnas.1615455113
发表时间：
2016-11-22
影响因子：
11.1
作者：
Cohen-Kaplan, Victoria;Livneh, Ido;Ciechanover, Aaron
通讯作者：
Ciechanover, Aaron
影响因子：
2.6
作者：
Houser, John R.;Ford, Eintou;Errede, Beverly
通讯作者：
Errede, Beverly
影响因子：
64.5
作者：
FINLEY, D;OZKAYNAK, E;VARSHAVSKY, A
通讯作者：
VARSHAVSKY, A
影响因子：
21.3
作者：
Cha-Molstad, Hyunjoo;Sung, Ki Sa;Hwang, Joonsung;Kim, Kyoung A.;Yu, Ji Eun;Yoo, Young Dong;Jang, Jun Min;Han, Dong Hoon;Molstad, Michael;Kim, Jung Gi;Lee, Yoon Jee;Zakrzewska, Adriana;Kim, Su-Hyeon;Kim, Sung Tae;Kim, Sun Yong;Lee, Hee Gu;Soung, Nak Kyun;Ahn, Jong Seog;Ciechanover, Aaron;Kim, Bo Yeon;Kwon, Yong Tae
通讯作者：
Kwon, Yong Tae