TIP30 induces apoptosis under oxidative stress through stabilization of p53 messenger RNA in human hepatocellular carcinoma

Details

Serval ID
serval:BIB_F7C49D8DA605
Type
Article: article from journal or magazin.
Collection
Publications
Title
TIP30 induces apoptosis under oxidative stress through stabilization of p53 messenger RNA in human hepatocellular carcinoma
Journal
Cancer Res
Author(s)
Zhao J., Chen J., Lu B., Dong L., Wang H., Bi C., Wu G., Guo H., Wu M., Guo Y.
ISSN
1538-7445 (Electronic)
ISSN-L
0008-5472
Publication state
Published
Issued date
2008
Volume
68
Number
11
Pages
4133-41
Language
english
Notes
Zhao, Jian
Chen, Jingjing
Lu, Bin
Dong, Li
Wang, Huajing
Bi, Chongshan
Wu, Guobin
Guo, Huaizu
Wu, Mengchao
Guo, Yajun
eng
Research Support, Non-U.S. Gov't
Cancer Res. 2008 Jun 1;68(11):4133-41. doi: 10.1158/0008-5472.CAN-08-0432.
Abstract
Reactive oxygen species (ROS) and cellular oxidant stress have long been associated with cancer. Here, we show that TIP30, also called CC3, regulates p53 mRNA stability and induces apoptosis by sensing of intracellular oxidative stress in human hepatocellular carcinoma (HCC) cells. Introduction of TIP30 induced more cell death in HepG2 cells with a high level of intracellular ROS than that in normal liver cell line, HL7702, which had low level of intracellular ROS. Treatment with an antioxidant agent attenuated TIP30-induced cell death in HepG2 cells, whereas oxidant H(2)O(2) augmented TIP30-induced cell death in HL7702 cells. The conformation of TIP30 was altered with the formation of an intermolecular disulfide bridge under oxidative stress. TIP30 greatly enhanced p53 expression and its transcriptional activity under oxidative stress, which was probably through stabilization of p53 mRNA. TIP30 induced apoptosis and mitochondrial dysfunction were blocked by silencing of p53 expression. The nuclear import of mRNA-binding protein HuR was blocked upon TIP30 introduction, which might be due to the interruption of the association of HuR with importin beta2. The elevated cytoplasmic HuR bound to p53 mRNA 3'-untranslated region, resulting in prolonged half-life of p53 mRNA. Our results suggest that TIP30 is involved in cellular oxidative stress surveillance and induces apoptosis through stabilization of p53 mRNA in HCC cells.
Keywords
Acetyltransferases/*physiology, Apoptosis/*physiology, Base Sequence, Carcinoma, Hepatocellular/genetics/metabolism/*pathology, Humans, Liver Neoplasms/genetics/metabolism/*pathology, *Oxidative Stress, RNA, Messenger/*genetics, RNA, Small Interfering, Transcription Factors/*physiology, Tumor Suppressor Protein p53/*genetics, Up-Regulation
Pubmed
Open Access
Yes
Create date
19/02/2018 0:04
Last modification date
20/08/2019 17:23
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