Ribosomal protein S29 regulates metabolic insecticide resistance through binding and degradation of CYP6N3.
Ribosomal protein S29 regulates metabolic insecticide resistance through binding and degradation of CYP6N3.
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DOI：
10.1371/journal.pone.0094611
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Zhu C
中科院分区：
文献类型：
--
作者：
Yu J;Hu S;Ma K;Sun L;Hu H;Zou F;Guo Q;Lei Z;Zhou D;Sun Y;Zhang D;Ma L;Shen B;Zhu C
许多疾病是通过蚊子传播的，包括疟疾、登革热、黄热病、丝虫病和西尼罗河热。化学防治在控制蚊媒疾病方面发挥着重要作用。然而，过度和持续使用杀虫剂已导致包括蚊子在内的许多物种对杀虫剂产生抗药性，这已成为控制蚊媒疾病的主要障碍。杀虫剂抗性是复杂的多基因遗传的结果，其机制尚不清楚。我们先前的研究发现核糖体蛋白RPS29与DM抵抗有关。在本研究中，我们旨在进一步研究RPS29与溴氰菊酯抗性的关系。在本研究中，串联亲和纯化被用来鉴定能够与RPS29相互作用的蛋白质。在候选蛋白中，通过GST下拉实验和免疫荧光实验，确定了CYP450超家族成员中的CYP6N3与RPS29结合。CCK-8法检测RPS29-CTP6N3相互作用与DM耐药的关系。CYP6N3过表达显著提高了昆虫细胞对DM的抗性和细胞活力，但RPS29过表达则逆转了这一作用。用Western印迹法研究了RPS29与细胞色素P6N3的相互作用机制。RPS29通过蛋白酶体促进CYP6N3蛋白降解。这些观察表明，一种新的RPS29相互作用伙伴--CYP6N3可以刺激蚊虫细胞对溴氰菊酯的抗性，并且针对CYP6N3的RPS29过表达可以降解蛋白酶体，消除与CYP6N3相关的对溴氰菊酯的抗性。我们的发现为细胞色素P450介导的糖尿病抵抗提供了一种新的机制。
Many diseases are transmitted by mosquitoes, including malaria, dengue fever, yellow fever, filariasis, and West Nile fever. Chemical control plays a major role in managing mosquito-borne diseases. However, excessive and continuous application of insecticides has caused the development of insecticide resistance in many species including mosquito, and this has become the major obstacle to controlling mosquito-borne diseases. Insecticide resistance is the result of complex polygenic inheritance, and the mechanisms are not well understood. Ribosomal protein RPS29 was found to be associated with DM resistance in our previous study. In this study, we aim to further investigate the involvement of RPS29 in deltamethrin resistance. In this study, tandem affinity purification was used to identify proteins that can interact with RPS29. Among the candidate proteins, CYP6N3, a member of the CYP450 superfamily, was identified, and binding to RPS29 was confirmed in vitro and in vivo by GST pull-down and immunofluorescence. CCK-8 assay was used to investigate the RPS29-CTP6N3 interaction in relation to DM resistance. CYP6N3 overexpression significantly enhanced DM resistance and insect cell viability, but this was reversed by RPS29 overexpression. Western blot was used to study the mechanism of interaction between RPS29 and CYP6N3. RPS29 increases CYP6N3 protein degradation through the proteasome. These observations indicate that CYP6N3, a novel RPS29-interacting partner, could stimulate deltamethrin resistance in mosquito cells and RPS29 overexpression targeted CYP6N3 for proteosomal degradation, abrogating the CYP6N3-associated resistence to deltamethrin. Our findings provide a novel mechanism associated with CYP450s mediated DM resistance.
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影响因子：
3.8
作者：
CARINO, FA;KOENER, JF;FEYEREISEN, R
通讯作者：
FEYEREISEN, R
影响因子：
20.1
作者：
Wang X;Pattison JS;Su H
通讯作者：
Su H
影响因子：
3.8
作者：
Liu, N;Scott, JG
通讯作者：
Scott, JG
现场捕获的耐氯菊酯抗蚊子冈比亚过表达CYP6P3，一种代谢拟除虫菊酯的P450。
影响因子：
4.5
作者：
Mueller, Pie;Warr, Emma;Stevenson, Bradley J.;Pignatelli, Patricia M.;Morgan, John C.;Steven, Andrew;Yawson, Alexander E.;Mitchell, Sara N.;Ranson, Hilary;Hemingway, Janet;Paine, Mark J. I.;Donnelly, Martin J.
通讯作者：
Donnelly, Martin J.
DOI：
10.1016/s0006-291x(03)00532-1
发表时间：
2003-04-25
影响因子：
3.1
作者：
Khanna, N;Sen, S;Singh, N
通讯作者：
Singh, N