Phosphorylation of PFKFB4 by PIM2 promotes anaerobic glycolysis and cell proliferation in endometriosis.
Phosphorylation of PFKFB4 by PIM2 promotes anaerobic glycolysis and cell proliferation in endometriosis.
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DOI：
10.1038/s41419-022-05241-6
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发表时间：
2022-09-15
影响因子：
9
通讯作者：
Yu, Zhenhai
中科院分区：
文献类型：
--
作者：
Lu, Chao;Qiao, Pengyun;Fu, Ruihai;Wang, Yadi;Lu, Jiayi;Ling, Xi;Liu, Lu;Sun, Yujun;Ren, Chune;Yu, Zhenhai
子宫内膜异位症（EM）是妇女慢性盆腔刺痛的常见原因之一，与不孕症密切相关。EM的长期、复杂、全身性和治疗后复发严重影响了女性的生活质量。在EM中发现了广泛的代谢重编程（有氧糖酵解、葡萄糖过量摄入和高乳酸生成）和癌症样变化，这与肿瘤发生有着惊人的相似之处。关键的糖酵解调节因子PFKFB4在EM中过表达。然而，PFKFB4在EM中的作用机制尚不清楚。我们发现PFKFB4表达上调，并且与EM的进展密切相关。我们发现focus PIM2是PFKFB4的一个新的先锋连接蛋白。我们用有力的生化方法证实了PIM2磷酸化了PFKFB4的Thr140位点。PIM2还可通过泛素-蛋白酶体途径增强PFKFB4蛋白的表达。此外，在子宫内膜异位症中，PIM2的表达确实与PFKFB4相对应。重要的是，PIM2磷酸化PFKFB4对Thr140的磷酸化促进了EM糖酵解和细胞生长。我们的研究表明，PIM2介导PFKFB4 Thr140磷酸化，从而调节糖酵解和EM进展。我们揭示了一个新的机制，即PIM2模拟了PFKFB4调控的中心上游伙伴关系，并揭示了PIM2-PFKFB4调控EM生长的新途径。我们的研究为进一步阐明EM糖代谢重编程提供了新的理论支持，并为探索EM的非避孕治疗提供了新的线索。
Endometriosis (EM) is one of the vanquished wonted causes of chronic pelvic sting in women and is closely associated with infertility. The long-term, complex, systemic, and post-treatment recurrence of EM wreaks havoc on women’s quality of life. Extensive metabolic reprogramming (aerobic glycolysis, glucose overweening intake, and high lactate production) and cancer-like changes have been found in EM, which bears striking similarities to tumorigenesis. The key glycolysis regulator PFKFB4 is overexpressed in EM. However, the mechanism of PFKFB4 in EM remains unknown. We found that PFKFB4 was upregulated and was closely related to the progression of EM. We identified focus PIM2 as a new pioneering adjoin protein of PFKFB4. Vigorous biochemical methods were used to confirm that PIM2 phosphorylated site Thr140 of PFKFB4. PIM2 also could enhance PFKFB4 protein expression through the ubiquitin–proteasome pathway. Moreover, PIM2 expression was really corresponding prevalent with PFKFB4 in endometriosis in vivo. Importantly, phosphorylation of PFKFB4 on Thr140 by PIM2 promoted EM glycolysis and cell growth. Our study demonstrates that PIM2 mediates PFKFB4 Thr140 phosphorylation thus regulating glycolysis and EM progression. We illustrated a new mechanism that PIM2 simulated a central upstream partnership in the regulation of PFKFB4, and reveal a novel means of PIM2-PFKFB4 setting EM growth. Our research provided new theoretical support for further clarifying the reprogramming of EM glucose metabolism, and provided new clues for exploring non-contraceptive treatments for EM.
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影响因子：
4.8
作者：
Krikun, G;Mor, G;Lockwood, CJ
通讯作者：
Lockwood, CJ
影响因子：
7
作者：
Liang Z;Wu Q;Wang H;Tan J;Wang H;Gou Y;Cao Y;Li Z;Zhang Z
通讯作者：
Zhang Z
影响因子：
3.1
作者：
Meng J;Chen X;Han Z
通讯作者：
Han Z
影响因子：
5.2
作者：
Lu, Chao;Ren, Chune;Yu, Zhenhai
通讯作者：
Yu, Zhenhai
影响因子：
4.4
作者：
Atkins, Hannah M.;Bharadwaj, Manish S.;Caudell, David L.
通讯作者：
Caudell, David L.