Stabilization of p21 (Cip1/WAF1) following Tip60-dependent acetylation is required for p21-mediated DNA damage response

M. S. Lee, J. Seo, D. Y. Choi, E. W. Lee, A. Ko, N. C. Ha, J. Bok Yoon, H. W. Lee, K. Pyo Kim, J. Song

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)620-629
Number of pages10
JournalCell Death and Differentiation
Volume20
Issue number4
DOIs
Publication statusPublished - 2013 Apr 1

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Acetylation
DNA Damage
Cell Cycle Checkpoints
Cell Aging
Post Translational Protein Processing
Doxorubicin
Lysine
Mass Spectrometry
Cell Cycle
Amino Acids
Antibodies

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Cite this

Lee, M. S. ; Seo, J. ; Choi, D. Y. ; Lee, E. W. ; Ko, A. ; Ha, N. C. ; Bok Yoon, J. ; Lee, H. W. ; Pyo Kim, K. ; Song, J. / Stabilization of p21 (Cip1/WAF1) following Tip60-dependent acetylation is required for p21-mediated DNA damage response. In: Cell Death and Differentiation. 2013 ; Vol. 20, No. 4. pp. 620-629.
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Stabilization of p21 (Cip1/WAF1) following Tip60-dependent acetylation is required for p21-mediated DNA damage response. / Lee, M. S.; Seo, J.; Choi, D. Y.; Lee, E. W.; Ko, A.; Ha, N. C.; Bok Yoon, J.; Lee, H. W.; Pyo Kim, K.; Song, J.

In: Cell Death and Differentiation, Vol. 20, No. 4, 01.04.2013, p. 620-629.

Research output: Contribution to journalArticle

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AU - Ko, A.

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AU - Song, J.

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