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Mitotic role of protein kinase PKM2 discovered


A study has demonstrated the role of the protein kinase PMK2 in controlling cell division; a discovery that could provide a molecular basis for tumor diagnosis and treatment. These results were featured recently in Nature Communications.

The research group, led by Zhimin Lu (The University of Texas MD Anderson Cancer Center, TX, USA), have previously reported PKM2’s ability to control gene expression by binding to transcriptional factors and phosphorylating histone.

“PKM2 is expressed at high levels during tumor progression and is important for cell growth. However, there’s been little information about whether it directly controls cell division,” explained Lu. “Our findings underscored its function in tumor formation during the final stages of cell division known as cytokinesis.”

The team utilized mice to study the role of PKM2 in the development of brain tumors. By examining the protein-coding gene MLC2, the team were able to detect how phosphorylation of MLC2 by PKM2 transpires. Upon phosphorylation of MCL2, the parent cell is able to separate into two ‘daughter’ cells. Understanding the molecular control of cytokinesis is particularly important due to the role of cell division in tumor initiation and propagation.

“The results revealed that PKM2-regulated MLC2 phosphorylation and the related cytokinesis are instrumental in brain tumor development and are found to precisely control cell division,” remarked Lu. “More importantly, our research shows that PKM2-regulated cytokinesis occurs in malignant tumors with bad outcome, such as glioblastoma, pancreatic cancer and melanoma.”

If certain protein-coding genes (for example, EGFR, B-Raf and K-Ras) are activated, tumors cells generate new ‘molecular signatures’ for the regulation of cell proliferation. These changes allow the tumor cells to synchronize their metabolism and cell progression through PKM2.

Source: The University of Texas MD Anderson Cancer Center press release