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Selective inhibition of histone deacetylase 2 induces p53-dependent survivin downregulation through MDM2 proteasomal degradation

Authors
 Sung-Keum Seo  ;  Chang-Sun Hwang  ;  Tae-Boo Choe  ;  Seok-Il Hong  ;  Jae Youn Yi  ;  Sang-Gu Hwang  ;  Hyun-Gyu Lee  ;  Sang Taek Oh  ;  Yun-Han Lee  ;  In-Chul Park 
Citation
 Oncotarget, Vol.6(28) : 26528-26540, 2015 
Journal Title
 Oncotarget 
ISSN
 1949-2553 
Issue Date
2015
Abstract
In the present study, we found that selective inhibition of histone deacetylase 2 (HDAC2) with small inhibitory RNA (siRNA) induced survivin downregulation in a p53-dependent manner. Interestingly, suberoylanilide hydroxamic acid (SAHA) or knockdown of HDAC2 induced downregulation of Mdm2, a negative regulator of p53, at the protein level. SAHA and/or HDAC2 siRNA increased Mdm2 ubiquitination, and MG132, an inhibitor of proteosome function, prevented HDAC2 inhibition-induced degradation of Mdm2. Clinically, the mRNA levels of HDAC2 and survivin were prominently overexpressed in lung cancer patients compared to normal lung tissues. Silencing of HDAC2 enhanced the cell death caused by ionizing radiation in lung cancer cells. Collectively, our results indicate that selective inhibition of HDAC2 causes survivin downregulation through activation of p53, which is mediated by downregulation of Mdm2. They further suggest that HDAC2 may exert a dominant effect on lung cancer cell survival by sustaining Mdm2-survivin levels.
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/141650
DOI
10.18632/oncotarget.3100
Appears in Collections:
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Radiation Oncology (방사선종양학교실)
Yonsei Authors
이윤한(Lee, Yun Han)
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