The molecular mechanisms controlling post-translational modifications of p21 have been pursued assiduously in recent years. Here, utilizing mass-spectrometry analysis and site-specific acetyl-p21 antibody, two lysine residues of p21, located at amino-acid sites 161 and 163, were identified as Tip60-mediated acetylation targets for the first time. Detection of adriamycin-induced p21 acetylation, which disappeared after Tip60 depletion with concomitant destabilization of p21 and disruption of G1 arrest, suggested that Tip60-mediated p21 acetylation is necessary for DNA damage-induced cell-cycle regulation. The ability of 2KQ, a mimetic of acetylated p21, to induce cell-cycle arrest and senescence was significantly enhanced in p21 null MEFs compared with those of cells expressing wild-type p21. Together, these observations demonstrate that Tip60-mediated p21 acetylation is a novel and essential regulatory process required for p21-dependent DNA damage-induced cell-cycle arrest.
Bibliographical noteFunding Information:
Acknowledgements. This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MEST) (2010-0017787), a grant of the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (A110961) and WCU (World Class University) program (Project No. R33-10128) through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science, and Technology.
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Cell Biology