Chinese Journal of Magnetic Resonance ›› 2022, Vol. 39 ›› Issue (1): 87-95.doi: 10.11938/cjmr20212901

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The Effect of T69E-mimicked Phosphorylation on the Interaction Between Bcl-2 and Nur77

Qian XU1,2,Lang CHEN1,2,Xiang-ying HU1,Cong-gang LI1,Yi-xiang LIU1,*(),Ling JIANG1,*()   

  1. 1. CAS Key Laboratory of Magnetic Resonance in Biological System, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Center for Magnetic Resonance in Wuhan, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences, Wuhan 430071, China
    2. University of Chinese Academy of Sciences, Beijing 100049, China
  • Received:2021-03-24 Online:2022-03-05 Published:2021-04-09
  • Contact: Yi-xiang LIU,Ling JIANG E-mail:yixiangliu@wipm.ac.cn;lingjiang@wipm.ac.cn

Abstract:

Bcl-2 mainly executes anti-apoptotic function in the Bcl-2 family. Nuclear orphan receptor Nur77 can be translocated from nucleus to mitochondria, then interact with Bcl-2 to reverse the function of Bcl-2 from a cell protector to a cell killer, thereby inducing cell apoptosis. The function of Bcl-2 is regulated by post-translational modification, such as the phosphorylation of T69 in the intrinsically disordered loop between BH3 and BH4 motifs. However, due to the lack of structural information of the full-length protein, the effect of phosphorylation modification of T69 in the loop region on the interaction of the two proteins is still unclear, and there is a lack of related research at the atomic level. Therefore, we constructed a full-length intracellular Bcl-2 containing loop region and T69E mutant to mimic stable phosphorylation modification, and investigated the interactions by combining circular dichroism (CD), Western blot and nuclear magnetic resonance (NMR) methods. It was observed that the full-length Bcl-2 had a stronger interaction with Nur77 compared to the Bcl-2/xl chimera, and the phosphorylation modification mimicked by T69E weakened the interaction between Bcl-2 and Nur77. The results will promote future research based on Bcl-2 and Nur77 signal transduction pathways and the apoptosis targeting cancer cells.

Key words: Bcl-2, nuclear magnetic resonance (NMR), phosphorylation, protein-protein interaction, apoptosis factor

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