Gastric cancer (GC) is one of the main causes of cancer-related death. Lysine acetyltransferases 2 A (KAT2A) is a succinyltransferase that plays an essential role in cancer development. The pyruvate kinase M2 (PKM2) is a glycolysis rate-limiting enzyme that mediates the glycolysis of cancers. This study aimed to explore the effects and mechanism of KAT2A in GC progression. The effects of biological behaviors of GC cells were evaluated by MTT, colony formation and seahorse assays. The succinylation modification was assessed by immunoprecipitation (IP). The interaction between proteins were detected by Co-IP and immunofluorescence. A pyruvate kinase activity detection kit was used to evaluate the activity of PKM2. Western blot was performed to detect the expression and oligomerization of protein. Herein, we confirmed that KAT2A was highly expressed in GC tissues and was associated with a poor prognosis. Function studies showed that knockdown of KAT2A inhibited cell proliferation and glycolytic metabolism of GC. Mechanistically, KAT2A could directly interacted with PKM2 and KAT2A silencing inhibited the succinylation of PKM2 at K475 site. In addition, the succinylation of PKM2 altered its activity rather than its protein levels. Rescue experiments showed that KAT2A promoted GC cell growth, glycolysis, and tumor growth by promoting PKM2 K475 succinylation. Taken together, KAT2A promotes the succinylation of PKM2 at K475 to inhibit PKM2 activity, thus promotes the progression of GC. Therefore, targeting KATA2 and PKM2 may provide novel strategies for the treatment of GC.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1007/s12033-023-00778-z | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Role in posttranslational modification of M2type pyruvate kinase in tumorigenesis and development.
Zhong Nan Da Xue Xue Bao Yi Xue Ban
December 2023
Laboratory of Tumor Molecular Biology, Research Institute of Medicine and Pharmacy, Qiqihar Medical University, Qiqihar Heilongjiang 161006, China.
PKM2, also known as M2-type pyruvate kinase, has attracted significant attention due to its crucial role in glycolysis and its abnormal expression in various tumors. With the discovery of PKM2's non-metabolic functions, the transition between its pyruvate kinase activity (in the tetrameric form in the cytoplasm) and protein kinase activity (in the dimeric form in the nucleus) has once again made PKM2 a target of interest in cancer research. Studies have shown that PKM2 is a protein susceptible to various post-translational modifications, and different post-translational modifications play important regulatory roles in processes such as PKM2 cellular localization, structure, and enzyme activity conversion.
View Article and Find Full Text PDFKAT2A Promotes the Succinylation of PKM2 to Inhibit its Activity and Accelerate Glycolysis of Gastric Cancer.
Mol Biotechnol
June 2024
Department of General Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, Guangdong, China.
Gastric cancer (GC) is one of the main causes of cancer-related death. Lysine acetyltransferases 2 A (KAT2A) is a succinyltransferase that plays an essential role in cancer development. The pyruvate kinase M2 (PKM2) is a glycolysis rate-limiting enzyme that mediates the glycolysis of cancers.
View Article and Find Full Text PDFPosttranslational modification of pyruvate kinase type M2 (PKM2): novel regulation of its biological roles to be further discovered.
J Physiol Biochem
August 2021
Clinical Medical Research Institute, First Affiliated Hospital of Xinjiang Medical University, Xinjiang Uygur Autonomous Region, Urumqi, People's Republic of China.
PKM2, pyruvate kinase type M2, has been shown to play a key role in aerobic glycolysis and to regulate the malignant behaviors of cancer cells. Recently, PKM2 has been revealed to hold dual metabolic and nonmetabolic roles. Working as both a pyruvate kinase with catalytic activity and a protein kinase that phosphorylates its substrates, PKM2 stands at the crossroads of glycolysis and tumor growth.
View Article and Find Full Text PDFHybridSucc: A Hybrid-learning Architecture for General and Species-specific Succinylation Site Prediction.
Genomics Proteomics Bioinformatics
April 2020
Department of Bioinformatics and Systems Biology, Key Laboratory of Molecular Biophysics of the Ministry of Education, Hubei Bioinformatics and Molecular Imaging Key Laboratory, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China; Huazhong University of Science and Technology Ezhou Industrial Technology Research Institute, Ezhou 436044, China. Electronic address:
As an important protein acylation modification, lysine succinylation (Ksucc) is involved in diverse biological processes, and participates in human tumorigenesis. Here, we collected 26,243 non-redundant known Ksucc sites from 13 species as the benchmark data set, combined 10 types of informative features, and implemented a hybrid-learning architecture by integrating deep-learning and conventional machine-learning algorithms into a single framework. We constructed a new tool named HybridSucc, which achieved area under curve (AUC) values of 0.
View Article and Find Full Text PDFSuccinylation-dependent mitochondrial translocation of PKM2 promotes cell survival in response to nutritional stress.
Cell Death Dis
February 2019
Institute of Systems Biomedicine, Peking University Health Science Center, Beijing, 100191, China.
Tumor growth and progression is characteristically associated with the synergistic effects of uncontrolled cellular proliferation and cell survival under stress. Pyruvate kinase M2 (PKM2) contributes to both of these effects. However, the specific mechanism by which PKM2 promotes uncontrolled proliferation or cell survival under stress in different nutritional environments is unclear.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!