Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Liver Kinase B1 Mediates Its Anti-Tumor Function by Binding to the N-Terminus of Malic Enzyme 3

  • Seung Bae Rho (Division of Cancer Biology, Research Institute, National Cancer Center) ;
  • Hyun Jung Byun (College of Pharmacy, Dongguk University) ;
  • Boh-Ram Kim (College of Pharmacy, Dongguk University) ;
  • Chang Hoon Lee (College of Pharmacy, Dongguk University)
  • Received : 2023.03.01
  • Accepted : 2023.03.24
  • Published : 2023.05.01
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Abstract

Liver kinase B1 (LKB1) is a crucial tumor suppressor involved in various cellular processes, including embryonic development, tumor initiation and progression, cell adhesion, apoptosis, and metabolism. However, the precise mechanisms underlying its functions remain elusive. In this study, we demonstrate that LKB1 interacts directly with malic enzyme 3 (ME3) through the N-terminus of the enzyme and identified the binding regions necessary for this interaction. The binding activity was confirmed to promote the expression of ME3 in an LKB1-dependent manner and was also shown to induce apoptosis activity. Furthermore, LKB1 and ME3 overexpression upregulated the expression of tumour suppressor proteins (p53 and p21) and downregulated the expression of antiapoptotic proteins (nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and B-cell lymphoma 2 (Bcl-2)). Additionally, LKB1 and ME3 enhanced the transcription of p21 and p53 and inhibited the transcription of NF-κB. Moreover, LKB1 and ME3 suppressed the phosphorylation of various components of the phosphatidylinositol-4,5-bisphosphate 3-kinase/protein kinase B signaling pathway. Overall, these results suggest that LKB1 promotes pro-apoptotic activities by inducing ME3 expression.

Keywords

Acknowledgement

This work was supported by a grant from the National Cancer Center, Korea (NCC-2112500-1 and 2210450-1) and the Basic Science Research Program and the BK21 FOUR program through the NRF (NRF-2018R1A5A2023127, and NRF-2020R1A2C3004973).

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