肝激酶B1（LKB1）是与胚胎发育、肿瘤起始和进展、细胞粘附、凋亡和代谢等多种细胞过程有关的关键肿瘤抑制剂。然而，其功能的确切机制仍不清楚。在本研究中，我们展示了LKB1通过酶的N-末端与苹果酸酶3（ME3）直接相互作用，并确定了该相互作用所需的结合区域。验证了该结合活性以一种依赖于LKB1的方式促进了ME3的表达，并显示出诱导凋亡活性。此外，LKB1和ME3的过表达上调了肿瘤抑制蛋白（p53和p21）的表达，并下调了抗凋亡蛋白（核因子kappaB轻链增强剂激活B细胞（NF-κB）和B细胞淋巴瘤2蛋白（Bcl-2））的表达。此外，LKB1和ME3增强了p21和p53的转录，并抑制了NF-κB的转录。此外，LKB1和ME3抑制了磷脂酰肌醇-4，5-双磷酸3-激酶/蛋白激酶B信号通路的各个组分的磷酸化。总的来说，这些结果表明，LKB1通过诱导ME3表达促进了促凋亡活性。

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.