Arrest Defective 1 Autoacetylation Is a Critical Step in Its Ability to Stimulate Cancer Cell Proliferation

作者：Seo Ji Hae; Cha Jong Ho; Park Ji Hyeon; Jeong Chul Ho; Park Zee Yong; Lee Hye Suk; Oh Seung Hyun; Kang Ju Hee; Suh Se Won; Kim Kyoung Hoon; Ha Jun Yong; Han Sang Hee; Kim Se Hee; Lee Ji Won; Park Jeong Ae; Jeong Joo Won; Lee Kong Joo; Oh Goo Taeg; Lee Mi Ni; Kwon Sung Won; Lee Seung Ki; Chun Kwang Hoon; Lee Su Jae; Kim Kyu Won^*

来源：Cancer Research, 2010, 70(11): 4422-4432.

DOI：10.1158/0008-5472.CAN-09-3258

The N-acetyltransferase arrest defective 1 (ARD1) is an important regulator of cell growth and differentiation that has emerged recently as a critical molecule in cancer progression. However, the regulation of the enzymatic and biological activities of human ARD1 (hARD1) in cancer is presently poorly understood. Here, we report that hARD1 undergoes autoacetylation and that this modification is essential for its functional activation. Using liquid chromatography-tandem mass spectrometry and site-directed mutational analyses, we identified K136 residue as an autoacetylation target site. K136R mutation abolished the ability of hARD1 to promote cancer cell growth in vitro and tumor xenograft growth in vivo. Mechanistic investigations revealed that hARD1 autoacetylation stimulated cyclin D1 expression through activation of the transcription factors beta-catenin and activator protein-1. Our results show that hARD1 autoacetylation is critical for its activation and its ability to stimulate cancer cell proliferation and tumorigenesis. Cancer Res; 70(11); 4422-32.

• 出版日期2010-6-1