ARD1 regulates cell cycle via Aurora kinase A
- 약학대학 약학과
- Issue Date
- 서울대학교 대학원
- 학위논문 (석사)-- 서울대학교 대학원 : 약학과, 2014. 2. 김규원.
- ARD1 (N-acetyltransferase arrest defective 1) is first identified to have N-α-acetylation activity in yeast and classified as a subunit of NatA acetyltransferase. It is also reported to catalyze both N-α-acetylation and N-ε-acetylation in mammalian cells. ARD1 overexpression has been found in many cancers such as breast cancer, prostate cancer, lung cancer, cervical cancer. It has been considered as an critical molecule in cell proliferation. The autoacetylation activity of ARD1 has been discovered as a key regulator of cell cycle. However, the biological mechanism of ARD1 in cell cycle hasn’t been well-defined yet. Whereas Aurora kinase A (AURKA) is a member of Aurora kinase protein family, Aurora kinase A is known as serine/threonine-protein kinase 6 and involved in centrosome maturation, separation as well as mitotic spindle assembly. Therefore, Aurora kinase A has a very important role in regulation of cell cycle. Recent studies revealed that Aurora kinase A overexpression is correlated with aneuploidy, supernumerary centrosomes, defective mitotic spindle and has been seen in some cancers, including breast, prostate, ovarian, cervical, and colorectal cancer. We found that ARD1 localizes to the centrosome during mitotic phases. Immunoprecipitation assays indicated that Aurora kinase A is an ARD1 binding partner. Furthermore, Aurora kinase A was seen to be acetylated by in vitro acetylation assay. In addition, cell proliferation was seen in overexpressed ARD1 WT but not its mutants. Taken together, these results suggest that the acetylation activity of ARD1 is related to cell cycle regulation possibly via Aurora kinase A.