Phosphorylated YBX2 is stabilized to promote glycolysis in brown adipocytes.
Phosphorylated YBX2 is stabilized to promote glycolysis in brown adipocytes.
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DOI：
10.1016/j.isci.2023.108091
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发表时间：
2023-10-20
期刊：
影响因子：
5.8
通讯作者：
Pan, Dongning
中科院分区：
文献类型：
--
作者：
Zhao, Qingwen;Yu, Chao;Xu, Xiaoxuan;Jin, Wenfang;Zhang, Zhe;Huang, Haiyan;Gao, Yue;Pan, Dongning
Y-box结合蛋白2(YBX2)是棕色脂肪组织激活的重要调节因子，但其自身表达的调控及相关机制目前仍不清楚。在这里，我们报告了YBX2蛋白水平，而不是基因水平，是对急性β-肾上腺素能信号的反应。在这种情况下，YBX2是AMPK和Akt2的双重底物。AMPK在Thr115处或Akt2在Ser137处的磷酸化通过减少泛素化介导的降解来促进YBX2在棕色脂肪细胞中的积累。除了稳定PGC1YBX2基因的表达外，在热源激活时增加α还有助于糖酵解酶的表达，促进葡萄糖的利用和乳酸的产生。在机制上，YBX2通过直接与糖酵解基因的5‘-UTRs结合来调节这些基因的翻译。综上所述，这些发现表明YBX2通过磷酸化修饰对生热刺激做出反应，稳定的YBX2有助于促进棕色脂肪细胞的糖酵解和产热。AMPK和Akt2分别在Thr115和Ser137处磷酸化YBX2，抑制其泛素介导的降解YBX2通过与糖酵解基因的5‘-UTR结合促进糖酵解基因的翻译人类代谢；细胞生物学
Y-box binding protein 2 (YBX2) is an essential modulator of brown adipose tissue activation, yet the regulation on its own expression and the involved mechanism remains largely unknown. Herein, we report the YBX2 protein level, but not mRNA level, is induced in response to acute β-adrenergic signaling. In this context, YBX2 is a dual substrate for both AMPK and Akt2. The phosphorylation at Thr115 by AMPK or at Ser137 by Akt2 facilitates YBX2 accumulation in brown adipocytes by decreasing ubiquitination-mediated degradation. Beyond stabilizing PGC1α mRNA, increased YBX2 upon thermogenic activation assists the expression of glycolytic enzymes, promotes glucose utilization and lactate production. Mechanistically, YBX2 modulates translation of glycolytic genes via direct binding to 5′-UTRs of these genes. Together these findings suggest YBX2 is responsive to thermogenic stimuli by phosphorylation modification, and stabilized YBX2 helps to boost glycolysis and thermogenesis in brown adipocytes. AMPK and Akt2 phosphorylate YBX2 at Thr115 and Ser137, respectively Phosphorylation on YBX2 retards its ubiquintination-mediated degradation YBX2 promotes translation of glycolytic genes by binding to their 5′-UTR Human metabolism; Cell biology
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DOI：
10.1038/nrm.2016.96
发表时间：
2016-11
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
Wang W;Seale P
通讯作者：
Seale P
影响因子：
29
作者：
Kajimura S;Spiegelman BM;Seale P
通讯作者：
Seale P
影响因子：
11.8
作者：
Pan D;Huang L;Zhu LJ;Zou T;Ou J;Zhou W;Wang YX
通讯作者：
Wang YX
影响因子：
5.3
作者：
Evdokimova, V;Ruzanov, P;Sorensen, PHB
通讯作者：
Sorensen, PHB
影响因子：
82.9
作者：
Ikeda K;Kang Q;Yoneshiro T;Camporez JP;Maki H;Homma M;Shinoda K;Chen Y;Lu X;Maretich P;Tajima K;Ajuwon KM;Soga T;Kajimura S
通讯作者：
Kajimura S