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ARD1-mediated Aurora kinase A acetylation promotes cancer cell proliferation and migration

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Authors
보탐투이루
Advisor
Kyu-Won Kim
Major
약학대학 약학과
Issue Date
2017-08
Publisher
서울대학교 대학원
Keywords
ARD1Aurora kinase Alysine acetylationcell proliferationcell migration
Description
학위논문 (박사)-- 서울대학교 대학원 약학대학 약학과, 2017. 8. Kyu-Won Kim.
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. These findings indicate that ARD1-mediated acetylation of AuA enhances cell proliferation and migration, and probably contributes to cancer development.
Language
English
URI
https://hdl.handle.net/10371/137017
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College of Pharmacy (약학대학)Dept. of Pharmacy (약학과)Theses (Ph.D. / Sc.D._약학과)
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