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O-GlcNAcylation of PFKFB3 is required for tumor cell proliferation under hypoxia by Lei, Yinrui; Chen, Tao; Li, Yeyi; Shang, Man; Zhang, Yan; Jin, Yuepeng; Yu, Qiujing; Guo, Fang; Wang, Ting is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.
What is O-GlcNAcylation of PFKFB3 is required for tumor cell proliferation under hypoxia about?
The protein O-GlcNAcylation catalysed by O-GlcNAc transferase (OGT) is tightly regulated by glucose availability. It is upregulated and essential for tumor cell proliferation under hypoxic conditions. However, the mechanism behind is still unclear. Here, we showed that the glycolytic regulator 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB3), which also promotes cell cycle progression in the nucleus, was O-GlcNAcylated in response to hypoxia. The O-GlcNAcylation of PFKFB3 could compete phosphorylation by hypoxia-activated ERK at the same modification site Ser172. Phosphorylated PFKFB3 could interact with the protein G3BP2 and retain in the cytosol; this in turn led to the accumulation of hypoxia-induced-P27 in the nucleus resulting in the cell cycle arrest. Such a pathway was compromised by high level of PFKFB3 O-GlcNAcylation in tumor cells contributing to cell cycle progression. Consistently, the PFKFB3-Ser172 phosphorylation level inversely correlated with the OGT level in pancreatic cancer patients. Our findings uncovered an O-GlcNAcylation mediated mechanism to promote tumor cell proliferation under metabolic stress, linking the aberrant OGT activity to tumorigene
Who reads O-GlcNAcylation of PFKFB3 is required for tumor cell proliferation under hypoxia?
It is typically read by researchers, students, and practitioners in Biochemistry, Genetics and Molecular Biology.
- Author
- Lei, Yinrui; Chen, Tao; Li, Yeyi; Shang, Man; Zhang, Yan; Jin, Yuepeng; Yu, Qiujing; Guo, Fang; Wang, Ting
- Publisher
- Nature Publishing Group; Springer Science and Business Media LLC; New York NY: Nature Pub. Group (ISSN 2157-9024)
- Published
- 2020
- Language
- EN
- Field
- Biochemistry, Genetics and Molecular Biology (Life Sciences)