ARD1-mediated aurora kinase A acetylation promotes cell proliferation and migration

// Tam Thuy Lu Vo 1 , Ji-Hyeon Park 1 , Ji Hae Seo 2 , Eun Ji Lee 1 , Hoon Choi 1 , Sung-Jin Bae 1 , Hoang Le 1 , Sunho An 1 , Hye Shin Lee 1 , Hee-Jun Wee 1 and Kyu-Won Kim 1, 3 1 SNU-Harvard NeuroVascular Protection Research Center, College of Pharmacy and The Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 08826, Korea 2 Department of Biochemistry, School of Medicine, Keimyung University, Daegu 42601, Korea 3 Crop Biotechnology Institute, GreenBio Science and Technology, Seoul National University, Pyeongchang 25354, Korea Correspondence to: Kyu-Won Kim, email: qwonkim@snu.ac.kr Keywords: aurora kinase A, ARD1, lysine acetylation, cell proliferation, cell migration Abbreviations: AuA: Aurora kinase A; ARD1: Arrest defective protein 1; D-box: destruction box; DAD: D-box activating domain. Received: May 04, 2017 Accepted: June 30, 2017 Published: July 18, 2017 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.