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

doi:10.1038/cdd.2012.159

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

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31 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 language	English
Pages (from-to)	620-629
Number of pages	10
Journal	Cell Death and Differentiation
Volume	20
Issue number	4
DOIs	https://doi.org/10.1038/cdd.2012.159
Publication status	Published - 2013 Apr

Bibliographical note

Funding Information:
The acetylation of p21 has often been suspected to be one of the main post-translational modification pathways of p21. Although this possibility has been supported by the results of previous investigations, the acetyltransferase has been unidentified, and thus the physiological importance remains unclear.

All Science Journal Classification (ASJC) codes

Molecular Biology
Cell Biology

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10.1038/cdd.2012.159

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

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.",

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

note = "Funding Information: The acetylation of p21 has often been suspected to be one of the main post-translational modification pathways of p21. Although this possibility has been supported by the results of previous investigations, the acetyltransferase has been unidentified, and thus the physiological importance remains unclear.",

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doi = "10.1038/cdd.2012.159",

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AU - Lee, M. S.

AU - Seo, J.

AU - Choi, D. Y.

AU - Lee, E. W.

AU - Ko, A.

AU - Ha, N. C.

AU - Bok Yoon, J.

AU - Lee, H. W.

AU - Pyo Kim, K.

AU - Song, J.

N1 - Funding Information: The acetylation of p21 has often been suspected to be one of the main post-translational modification pathways of p21. Although this possibility has been supported by the results of previous investigations, the acetyltransferase has been unidentified, and thus the physiological importance remains unclear.

PY - 2013/4

Y1 - 2013/4

N2 - 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.

AB - 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.

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

Abstract

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All Science Journal Classification (ASJC) codes

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