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Biochem Biophys Res Commun. 2017 Dec 9;494(1-2):51-56. doi: 10.1016/j.bbrc.2017.10.087. Epub 2017 Oct 18.

HDAC6 deficiency induces apoptosis in mesenchymal stem cells through p53 K120 acetylation.

Author information

1
Graduate School of Analytical Science and Technology, Chungnam National University, Daejeon, 305-764, Republic of Korea.
2
Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul, 151-921, South Korea.
3
Graduate School of Analytical Science and Technology, Chungnam National University, Daejeon, 305-764, Republic of Korea. Electronic address: jaeyoungkim@cnu.ac.kr.
4
Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul, 151-921, South Korea. Electronic address: cyjcow@snu.ac.kr.
5
Graduate School of Analytical Science and Technology, Chungnam National University, Daejeon, 305-764, Republic of Korea. Electronic address: leejooyong@cnu.ac.kr.

Abstract

The acetylation of p53 is critical in modulating its pro-apoptotic roles. However, its regulatory mechanism and physiological significance are unclear. Here, we show HDAC6 negatively regulates pro-apoptotic acetylation of p53 at lysine residue 120 (K120) in mesenchymal stem cells (MSCs). The loss of HDAC6 expression in MSCs increases K120 acetylation of p53, which is successfully reversed by the wild-type but not by catalytically dead HDAC6. Deletion of HDAC6 induces caspase-dependent apoptosis by promoting transactivation of Bax and suppression of Bcl-2. Moreover, HDAC6 deficiency leads to mitochondrial dysfunction characterized by aberrant reactive oxygen species production and defective oxidative phosphorylation, which is reversed by ectopic expression of wild-type or acetylation mimetic p53. This study demonstrates that HDAC6 is a critical regulator of a pro-apoptotic p53 K120 acetylation and mitochondrial function in MSCs, suggesting that the modulation of HDAC6 activity could be a novel approach to improve MSC- based therapies.

KEYWORDS:

Acetylation; Apoptosis; Histone deacetylase 6 (HDAC6); Mesenchymal stem cells (MSCs); Mitochondrial dysfunction; p53

PMID:
29054408
DOI:
10.1016/j.bbrc.2017.10.087
[Indexed for MEDLINE]

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