Arrest defective 1 autoacetylation is a critical step in its ability to stimulate cancer cell proliferation

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

Research output: Contribution to journalArticle

43 Scopus citations

Abstract

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 β-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.

Original languageEnglish (US)
Pages (from-to)4422-4432
Number of pages11
JournalCancer Research
Volume70
Issue number11
DOIs
StatePublished - Jun 1 2010

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Seo, J. H., Cha, J. H., Park, J. H., Jeong, C. H., Park, Z. Y., Lee, H. S., Oh, S. H., Kang, J. H., Suh, S. W., Kim, K. H., Ha, J. Y., Han, S. H., Kim, S. H., Lee, J. W., Park, J. A., Jeong, J. W., Lee, K. J., Oh, G. T., Lee, M. N., ... Kim, K. W. (2010). Arrest defective 1 autoacetylation is a critical step in its ability to stimulate cancer cell proliferation. Cancer Research, 70(11), 4422-4432. https://doi.org/10.1158/0008-5472.CAN-09-3258