Deacetylation of Ku70 by SIRT6 attenuates Bax-mediated apoptosis in hepatocellular carcinoma

Journal Article · Sat Apr 15 04:00:00 EDT 2017 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2017.02.111· OSTI ID:22696961

Tao, Na-Na; Ren, Ji-Hua ^[1]; Tang, Hua ^[1]; Ran, Long-Kuan ^[2]; Zhou, Hong-Zhong; Liu, Bo ^[1]; Huang, Ai-Long ^[1]; Chen, Juan ^[1]

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1. The Second Affiliated Hospital and the Key Laboratory of Molecular Biology of Infectious Diseases Designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing (China)
2. Department of Anesthesiology, Daping Hospital, Third Military Medical University, Chongqing (China)

SIRT6 is a class III histone deacetylase that has been implicated in HCC development. We previously reported that SIRT6 potentiated apoptosis evasion in hepatocellular carcinoma by inhibiting both Bax expression and mitochondrial translocalization. However, the mechanism underlying SIRT6-mediated inhibition of Bax mitochondrial localization remains elusive. In this study, we found that although SIRT6 had no effect on the expression level of Ku70, SIRT6 could interact with Ku70 and deacetylate it. The increased acetylation of Ku70 in SIRT6-depleted cells disrupt its interaction with Bax, which finally resulted in Bax mitochondrial translocalization. Furthermore, lysine K542 on Ku70 was the target for deacetylation by SIRT6. Ku70{sup K542Q} mutation abolished suppression of association between Ku70 and Bax and caused redistribution of Bax to the cytosol in SIRT6-depleted cells. Finally, Ku70{sup K542Q} mutation could reversed the inhibition of growth and apoptosis promotion mediated by SIRT6 silencing. Together, our findings revealed SIRT6 could block the mitochondrial translocation of Bax and decrease the apoptotic ratio of HCC cells by deacetylation of Ku70. SIRT6 may serve as a promising target for developing targeted therapies for HCC in the future. - Highlights: • SIRT6 could associate with and deacetylate Ku70 in HCC cells. • Deacetylated Ku70 could interact with Bax and block its translocation to mitochondria. • SIRT6 deacetylates Ku70 on the lysine 542. • Ku70{sup K542Q} mutation reverses the inhibition of proliferation and promotion of apoptosis which caused by SIRT6 suppression.

• OSTI ID: 22696961
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 4 Vol. 485; ISSN BBRCA9; ISSN 0006-291X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
APOPTOSIS
HEPATOMAS
INHIBITION
INTERACTIONS
MITOCHONDRIA
MUTANTS
MUTATIONS
PLANT GROWTH
TRANSLOCATION