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ERK7 通过抗合成代谢激酶协调控制肥胖和生长。

Coordinated control of adiposity and growth by anti-anabolic kinase ERK7.

机构信息

Molecular and Integrative Biosciences Research Programme, Faculty of Biological and Environmental Sciences, University of Helsinki, Helsinki, Finland.

Institute of Biotechnology, University of Helsinki, Helsinki, Finland.

出版信息

EMBO Rep. 2021 Feb 3;22(2):e49602. doi: 10.15252/embr.201949602. Epub 2020 Dec 28.

DOI:10.15252/embr.201949602
PMID:33369866
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7857433/
Abstract

Energy storage and growth are coordinated in response to nutrient status of animals. How nutrient-regulated signaling pathways control these processes in vivo remains insufficiently understood. Here, we establish an atypical MAP kinase, ERK7, as an inhibitor of adiposity and growth in Drosophila. ERK7 mutant larvae display elevated triacylglycerol (TAG) stores and accelerated growth rate, while overexpressed ERK7 is sufficient to inhibit lipid storage and growth. ERK7 expression is elevated upon fasting and ERK7 mutant larvae display impaired survival during nutrient deprivation. ERK7 acts in the fat body, the insect counterpart of liver and adipose tissue, where it controls the subcellular localization of chromatin-binding protein PWP1, a growth-promoting downstream effector of mTOR. PWP1 maintains the expression of sugarbabe, encoding a lipogenic Gli-similar family transcription factor. Both PWP1 and Sugarbabe are necessary for the increased growth and adiposity phenotypes of ERK7 loss-of-function animals. In conclusion, ERK7 is an anti-anabolic kinase that inhibits lipid storage and growth while promoting survival on fasting conditions.

摘要

能量储存和生长是协调响应动物的营养状态。营养调节信号通路如何在体内控制这些过程还知之甚少。在这里，我们确定了一种非典型的 MAP 激酶 ERK7，它是果蝇中脂肪和生长的抑制剂。ERK7 突变体幼虫表现出升高的三酰基甘油 (TAG) 储存和加速的生长速度，而过表达的 ERK7 足以抑制脂肪储存和生长。禁食会导致 ERK7 表达升高，而 ERK7 突变体幼虫在营养剥夺期间表现出生存能力受损。ERK7 在脂肪体中起作用，脂肪体是昆虫肝脏和脂肪组织的对应物，它控制染色质结合蛋白 PWP1 的亚细胞定位，PWP1 是 mTOR 的促进生长的下游效应物。PWP1 维持糖宝宝的表达，糖宝宝编码一个脂肪生成 Gli 类似家族转录因子。PWP1 和 Sugarbabe 对于 ERK7 功能丧失动物的生长和肥胖表型的增加都是必要的。总之，ERK7 是一种抗合成代谢的激酶，它抑制脂肪储存和生长，同时促进禁食条件下的生存。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27f1/7857433/00ac08359a38/EMBR-22-e49602-g009.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27f1/7857433/29cf3b46bfae/EMBR-22-e49602-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27f1/7857433/62536118f904/EMBR-22-e49602-g007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27f1/7857433/b68426d3b0cc/EMBR-22-e49602-g011.jpg
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