| Interaction between ZBP-89 and p53 mutants and its contribution to effects of HDACi on hepatocellular carcinoma. | |
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MedLine Citation:
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PMID: 22214764 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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ZBP-89, a zinc finger transcription factor, participates in histone deacetylases inhibitors (HDACi)-mediated growth arrest and apoptosis in cancer cells. p53 mutants may interact with ZBP-89 that transcriptionally regulates p21(Waf1) (p21). However, this interaction and its consequence in cancer treatments are poorly understood. In this study, we demonstrate that ZBP‑89 is essentially required in HDACi-mediated p21 upregulation in hepetocellular carcinoma (HCC). Overexpression of ZBP-89 protein enhanced the lethal effectiveness of Trichostatin A (TSA). p53 mutant p53(G245D), but not p53(R249S), directly bound to ZBP-89 and prevented its translocation from cytoplasm to nucleus. Furthermore, p53(G245D) was shown to have a similar pattern of subcellular localization to ZBP-89 in tissues of HCC patients in Hong Kong. Functionally, the cytoplasmic accumulation of ZBP-89 by p53(G245D) significantly abrogated the induction of p21 caused by sodium butyrate (NaB) treatment and protected cells from TSA-induced death. The activations of several apoptotic proteins, such as Bid and PARP, were involved in p53(G245D)-mediated protection. Moreover, the resistance to HDACi in p53(G245D)-expressing cells was reversed by overexpression of ZBP-89. Taken together, these data suggest a potential mechanism via which mutant p53 enables tumor cells to resist chemotherapy and, therefore, establish a plausible link between mutant p53 binding to ZBP-89 and a decreased chemosensitivity of HCC cells. |
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Authors:
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Chris Z Y Zhang; George G Chen; Juanita L Merchant; Paul B S Lai |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2012-01-15 |
Journal Detail:
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Title: Cell cycle (Georgetown, Tex.) Volume: 11 ISSN: 1551-4005 ISO Abbreviation: Cell Cycle Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2012-02-06 Completed Date: 2012-08-30 Revised Date: 2013-05-06 |
Medline Journal Info:
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Nlm Unique ID: 101137841 Medline TA: Cell Cycle Country: United States |
Other Details:
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Languages: eng Pagination: 322-34 Citation Subset: IM |
Affiliation:
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Department of Surgery, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, NT Hong Kong. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Antineoplastic Agents
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pharmacology* Apoptosis Butyrates / pharmacology* Carcinoma, Hepatocellular / genetics, metabolism* Cell Line, Tumor / drug effects Cell Survival / drug effects Cyclin-Dependent Kinase Inhibitor p21 / metabolism DNA-Binding Proteins / genetics, metabolism* Drug Resistance, Neoplasm G1 Phase Cell Cycle Checkpoints / drug effects Gene Expression Histone Deacetylase Inhibitors / pharmacology* Humans Hydroxamic Acids / pharmacology* Mutant Proteins / genetics, metabolism* Mutation, Missense Protein Binding Transcription Factors / genetics, metabolism* Tumor Suppressor Protein p53 / genetics, metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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R01 DK055732/DK/NIDDK NIH HHS; R01-DK055732/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents; 0/Butyrates; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/DNA-Binding Proteins; 0/Histone Deacetylase Inhibitors; 0/Hydroxamic Acids; 0/Mutant Proteins; 0/TP53 protein, human; 0/Transcription Factors; 0/Tumor Suppressor Protein p53; 0/ZNF148 protein, human; 3X2S926L3Z/trichostatin A |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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