Stability of the Endosomal Scaffold Protein LAMTOR3 Depends on Heterodimer Assembly and Proteasomal Degradation
Stability of the Endosomal Scaffold Protein LAMTOR3 Depends on Heterodimer Assembly and Proteasomal Degradation
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DOI：
10.1074/jbc.m112.349480
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发表时间：
2013-06-21
影响因子：
4.8
通讯作者：
Huber, Lukas A.
中科院分区：
文献类型：
--
作者：
de Araujo, Mariana E. G.;Stasyk, Taras;Huber, Lukas A.
LAMTOR 3（MP 1）和LAMTOR 2（p14）形成异二聚体，作为来自晚期内体/溶酶体的MAPK和mTOR 1信号传导所需的较大Ragulator复合物的一部分。在这里，我们表明，LAMTOR 2（p14）的损失导致在一个不稳定的胞质单体池LAMTOR 3（MP 1）。单体细胞质LAMTOR 3以蛋白酶体依赖性但不依赖于溶酶体的方式快速降解。突变分析表明，该蛋白的周转依赖于几个赖氨酸残基的泛素化。类似地，其他Ragulator亚基LAMTOR 1（p18）、LAMTOR 4（c7 orf 59）和LAMTOR 5（HBXIP）也在LAMTOR 2缺失时降解。因此，通过细胞质量控制系统监测Ragulator复合物的组装，最有可能防止由有缺陷的Ragulator复合物引起的mTOR和MAPK会聚时的异常信号传导。
LAMTOR3 (MP1) and LAMTOR2 (p14) form a heterodimer as part of the larger Ragulator complex that is required for MAPK and mTOR1 signaling from late endosomes/lysosomes. Here, we show that loss of LAMTOR2 (p14) results in an unstable cytosolic monomeric pool of LAMTOR3 (MP1). Monomeric cytoplasmic LAMTOR3 is rapidly degraded in a proteasome-dependent but lysosome-independent manner. Mutational analyses indicated that the turnover of the protein is dependent on ubiquitination of several lysine residues. Similarly, other Ragulator subunits, LAMTOR1 (p18), LAMTOR4 (c7orf59), and LAMTOR5 (HBXIP), are degraded as well upon the loss of LAMTOR2. Thus the assembly of the Ragulator complex is monitored by cellular quality control systems, most likely to prevent aberrant signaling at the convergence of mTOR and MAPK caused by a defective Ragulator complex.