Autoacetylation regulates differentially the roles of ARD1 variants in tumorigenesis

  • Authors:
    • Ji Hae Seo
    • Ji-Hyeon Park
    • Eun Ji Lee
    • Tam Thuy Lu Vo
    • Hoon Choi
    • Jae Kyung Jang
    • Hee-Jun Wee
    • Bum Ju Ahn
    • Jong-Ho Cha
    • Min Wook Shin
    • Kyu-Won Kim
  • View Affiliations

  • Published online on: October 17, 2014     https://doi.org/10.3892/ijo.2014.2708
  • Pages: 99-106
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Abstract

ARD1 is an acetyltransferase with several variants derived from alternative splicing. Among ARD1 variants, mouse ARD1225 (mARD1225), mouse ARD1235 (mARD1235), and human ARD1235 (hARD1235) have been the most extensively characterized and are known to have different biological functions. In the present study, we demonstrated that mARD1225, mARD1235, and hARD1235 have conserved autoacetylation activities, and that they selectively regulate distinct roles of ARD1 variants in tumorigenesis. Using purified recombinants for ARD1 variants, we found that mARD1225, mARD1235, and hARD1235 undergo similar autoacetylation with the target site conserved at the Lys136 residue. Moreover, functional investigations revealed that the role of mARD1225 autoacetylation is completely distinguishable from that of mARD1235 and hARD1235. Under hypoxic conditions, mARD1225 autoacetylation inhibited tumor angiogenesis by decreasing the stability of hypoxia-inducible factor-1α (HIF-1α). Autoacetylation stimulated the catalytic activity of mARD1225 to acetylate Lys532 of the oxygen-dependent degradation (ODD) domain of HIF-1α, leading to the proteosomal degradation of HIF-1α. In contrast, autoacetylation of mARD1235 and hARD1235 contributed to cellular growth under normoxic conditions by increasing the expression of cyclin D1. Taken together, these data suggest that autoacetylation of ARD1 variants differentially regulates angiogenesis and cell proliferation in an isoform-specific manner.
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January 2015
Volume 46 Issue 1

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APA
Seo, J.H., Park, J., Lee, E.J., Vo, T.L., Choi, H., Jang, J.K. ... Kim, K. (2015). Autoacetylation regulates differentially the roles of ARD1 variants in tumorigenesis. International Journal of Oncology, 46, 99-106. https://doi.org/10.3892/ijo.2014.2708
MLA
Seo, J. H., Park, J., Lee, E. J., Vo, T. L., Choi, H., Jang, J. K., Wee, H., Ahn, B. J., Cha, J., Shin, M. W., Kim, K."Autoacetylation regulates differentially the roles of ARD1 variants in tumorigenesis". International Journal of Oncology 46.1 (2015): 99-106.
Chicago
Seo, J. H., Park, J., Lee, E. J., Vo, T. L., Choi, H., Jang, J. K., Wee, H., Ahn, B. J., Cha, J., Shin, M. W., Kim, K."Autoacetylation regulates differentially the roles of ARD1 variants in tumorigenesis". International Journal of Oncology 46, no. 1 (2015): 99-106. https://doi.org/10.3892/ijo.2014.2708