Abstract
Aurora kinase A (AuA) is a prerequisite for centrosome maturation, separation, and mitotic spindle assembly, thus, it is essential for cell cycle regulation. Overexpression of AuA is implicated in poor prognosis of many types of cancer. However, the regulatory mechanisms underlying the functions of AuA are still not fully understood. Here, we report that AuA colocalizes with arrest defective protein 1 (ARD1) acetyltransferase during cell division and cell migration. Additionally, AuA is acetylated by ARD1 at lysine residues at positions 75 and 125. The double mutations at K75/K125 abolished the kinase activity of AuA. Moreover, the double mutant AuA exhibited diminished ability to promote cell proliferation and cell migration. Mechanistic studies revealed that AuA acetylation at K75/K125 promoted cell proliferation via activation of cyclin E/CDK2 and cyclin B1. In addition, AuA acetylation stimulated cell migration by activating the p38/AKT/MMP-2 pathway. Our findings indicate that ARD1-mediated acetylation of AuA enhances cell proliferation and migration, and probably contributes to cancer development.
Highlights
Defective control of cell proliferation is the main characteristic of cancer
These observations suggest that interaction between arrest defective protein 1 (ARD1) and Aurora kinase A (AuA) at the centrosome may play a critical role in cell growth and cell movement
We propose a mechanism by which AuA acetylation regulates cell proliferation and migration
Summary
Defective control of cell proliferation is the main characteristic of cancer. Cell division is rigorously controlled by complex signaling circuits. Cancer cells can sustain proliferative signaling themselves and can grow unstoppably. Another hallmark of cancer is cell migration [1]. Cell migration is a highly integrated process, and controlled by dynamic regulatory mechanisms [2]. Understanding the mechanisms of controlling cell proliferation and cell motility could open new horizons in cancer therapy
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