Arabidopsis SINAT Proteins Control Autophagy by Mediating Ubiquitylation and Degradation of ATG13[OPEN]
Arabidopsis SINAT Proteins Control Autophagy by Mediating Ubiquitylation and Degradation of ATG13[OPEN]
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拟南芥 SINAT 蛋白通过调节 ATG13 的泛素化和降解来控制自噬
DOI：
10.1105/tpc.19.00413
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发表时间：
2020-01-01
期刊：
影响因子：
11.6
通讯作者：
Xiao, Shi
中科院分区：
文献类型：
--
作者：
Qi, Hua;Li, Juan;Xiao, Shi
在真核生物中，自噬通过回收细胞质组分来维持细胞内稳态。自噬相关蛋白（ATGs）ATG 1和ATG 13形成调节自噬体形成的蛋白激酶复合物;然而，调节ATG 1和ATG 13的机制仍然知之甚少。在这里，我们表明，在不同的营养条件下，环型E3连接酶SEVEN在缺乏拟南芥1（SINAT 1），SINAT 2和SINAT 6控制ATG 1和ATG 13的稳定性和自噬动力学通过调节ATG 13泛素化在拟南芥（拟南芥）。在长期饥饿和恢复过程中，ATG 1和ATG 13通过26 S蛋白酶体途径降解。肿瘤坏死因子受体相关因子1a（TRAF 1a）和TRAF 1b在植物体内与ATG 13 a和ATG 13 b相互作用，并需要SINAT 1和SINAT 2在体内泛素化和降解ATG 13 s。此外，ATG 13 a蛋白的赖氨酸K607和K609有助于K48连接的泛素化和去稳定化，并抑制自噬。在饥饿条件下，SINAT 6与ATG 13竞争性相互作用并诱导自噬体生物合成。此外，在饥饿条件下，ATG 1促进TRAF 1a蛋白在体内的稳定性，表明自噬的反馈调节。与ATGs在自噬中的功能一致，atg 1a atg 1b atg 1c三重敲除突变体表现出过早的叶片衰老，对营养饥饿的超敏反应，以及TRAF 1a稳定性的降低。TRAF 1a和TRAF 1b具有双重功能，通过促进SINAT 1/SINAT 2或SINAT 6介导的蛋白水解或稳定ATG 13蛋白来调节自噬动力学。
In eukaryotes, autophagy maintains cellular homeostasis by recycling cytoplasmic components. The autophagy-related proteins (ATGs) ATG1 and ATG13 form a protein kinase complex that regulates autophagosome formation; however, mechanisms regulating ATG1 and ATG13 remain poorly understood. Here, we show that, under different nutrient conditions, the RING-type E3 ligases SEVEN IN ABSENTIA OF ARABIDOPSIS THALIANA1 (SINAT1), SINAT2, and SINAT6 control ATG1 and ATG13 stability and autophagy dynamics by modulating ATG13 ubiquitylation in Arabidopsis (Arabidopsis thaliana). During prolonged starvation and recovery, ATG1 and ATG13 were degraded through the 26S proteasome pathway. TUMOR NECROSIS FACTOR RECEPTOR ASSOCIATED FACTOR1a (TRAF1a) and TRAF1b interacted in planta with ATG13a and ATG13b and required SINAT1 and SINAT2 to ubiquitylate and degrade ATG13s in vivo. Moreover, lysines K607 and K609 of ATG13a protein contributed to K48-linked ubiquitylation and destabilization, and suppression of autophagy. Under starvation conditions, SINAT6 competitively interacted with ATG13 and induced autophagosome biogenesis. Furthermore, under starvation conditions, ATG1 promoted TRAF1a protein stability in vivo, suggesting feedback regulation of autophagy. Consistent with ATGs functioning in autophagy, the atg1a atg1b atg1c triple knockout mutants exhibited premature leaf senescence, hypersensitivity to nutrient starvation, and reduction in TRAF1a stability. Therefore, these findings demonstrate that SINAT family proteins facilitate ATG13 ubiquitylation and stability and thus regulate autophagy.TRAF1a and TRAF1b have dual functions in regulating the dynamics of autophagy by facilitating SINAT1/SINAT2 or SINAT6-mediated proteolysis or stabilization of ATG13 proteins.