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Mapping the Structure-Function Relationships of Disordered Oncogenic Transcription Factors Using Transcriptomic Analysis
Published on: June 27, 2020
The Oncogenic Functions of MASTL Kinase
Kamila Marzec1, Andrew Burgess1,2
1ANZAC Research Institute, University of Sydney, Sydney, NSW, Australia.
Abstract:
MASTL kinase is a master regulator of mitosis, essential for ensuring that mitotic substrate phosphorylation is correctly maintained. It achieves this through the phosphorylation of alpha-endosulfine and subsequent inhibition of the tumor suppressor PP2A-B55 phosphatase. In recent years MASTL has also emerged as a novel oncogenic kinase that is upregulated in a number of cancer types, correlating with chromosome instability and poor patient survival. While the chromosome instability is likely directly linked to MASTL's control of mitotic phosphorylation, several new studies indicated that MASTL has additional effects outside of mitosis and beyond regulation of PP2A-B55. These include control of normal DNA replication timing, and regulation of AKT/mTOR and Wnt/β-catenin oncogenic kinase signaling. In this review, we will examine the phenotypes and mechanisms for how MASTL, ENSA, and PP2A-B55 deregulation drives tumor progression and metastasis. Finally, we will explore the rationale for the future development of MASTL inhibitors as new cancer therapeutics.
Insights
MASTL kinase regulates mitosis and DNA replication. Its deregulation drives cancer progression and metastasis, suggesting MASTL inhibitors could be effective cancer therapeutics.
Area of Science:
- Cell Biology
- Molecular Oncology
- Biochemistry
Background:
- MASTL kinase is a key regulator of mitosis, controlling substrate phosphorylation via alpha-endosulfine and PP2A-B55 phosphatase inhibition.
- MASTL is increasingly recognized as an oncogenic kinase implicated in various cancers, linked to chromosomal instability and reduced patient survival.
Purpose of the Study:
- To review the multifaceted roles of MASTL, ENSA, and PP2A-B55 in tumor progression and metastasis.
- To explore the potential of targeting MASTL as a cancer therapeutic strategy.
Main Methods:
- Literature review of recent studies on MASTL function beyond mitosis.
- Analysis of MASTL's involvement in DNA replication timing and oncogenic signaling pathways (AKT/mTOR, Wnt/β-catenin).
Main Results:
- MASTL deregulation contributes to tumor progression and metastasis through mechanisms beyond mitotic control.
- MASTL influences DNA replication timing and activates key oncogenic signaling pathways.
Conclusions:
- Dysregulation of the MASTL-ENSA-PP2A-B55 axis is a significant driver of cancer.
- MASTL inhibitors represent a promising therapeutic avenue for cancer treatment.
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