| Downregulation of ANP32B, a novel substrate of caspase-3, enhances caspase-3 activation and apoptosis induction in myeloid leukemic cells. | |
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MedLine Citation:
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PMID: 20015864 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The acidic leucine-rich nuclear phosphoprotein 32 (ANP32)B has been reported to regulate gene expression by acting as a histone chaperone or modulate messenger RNA trafficking by serving as a HuR ligand. However, its exact cellular functions are poorly understood. By utilizing a proteomics-based approach, in this work, we identify that the human ANP32B protein is cleaved during apoptosis induction by NSC606985, a novel camptothecin analog. Further investigation shows that various apoptosis inducers cause a decrease of full-length ANP32B in multiple cell lines with a concomitant increase of an approximately 17 kDa fragment. The proteolytic cleavage of ANP32B is inhibited by a specific caspase-3 inhibitor Z-DEVD-fmk, and it cannot be seen in NSC606985-induced death of caspase-3-deficient MCF-7 cells. In vitro caspase cleavage assay and mutagenesis experiment reveal that ANP32B is a direct substrate of caspase-3 and it is primarily cleaved at the sequence of Ala-Glu-Val-Asp, after Asp-163. Additionally, the reduced expression of endogenous ANP32B by specific small interfering RNA enhances caspase-3 activation and apoptosis induction by NSC606985 and etoposide. These results suggest that ANP32B is a novel substrate for caspase-3 and acts as a negative regulator for apoptosis, the mechanism of which remains to be explored. |
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Authors:
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Shao-Ming Shen; Yun Yu; Ying-Li Wu; Jin-Ke Cheng; Li-Shun Wang; Guo-Qiang Chen |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-12-16 |
Journal Detail:
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Title: Carcinogenesis Volume: 31 ISSN: 1460-2180 ISO Abbreviation: Carcinogenesis Publication Date: 2010 Mar |
Date Detail:
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Created Date: 2010-03-05 Completed Date: 2010-04-14 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8008055 Medline TA: Carcinogenesis Country: England |
Other Details:
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Languages: eng Pagination: 419-26 Citation Subset: IM |
Affiliation:
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Institute of Health Science, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences-Shanghai Jiao-Tong University School of Medicine, No. 280, Chong-Qing South Road, Shanghai 200025, China. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Acetophenones
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pharmacology Antineoplastic Agents / pharmacology Apoptosis / drug effects, physiology* Benzopyrans / pharmacology Camptothecin / analogs & derivatives, pharmacology Carcinoma / metabolism, pathology* Caspase 3 / metabolism* Cell Line, Tumor / drug effects, metabolism Cysteine Proteinase Inhibitors / pharmacology Down-Regulation Enzyme Activation Female Humans Leukemia, Myeloid / metabolism, pathology* Male Neoplasm Proteins / genetics, metabolism* Neoplasms / metabolism, pathology Nuclear Proteins / antagonists & inhibitors, genetics, metabolism* RNA Interference RNA, Small Interfering / pharmacology Recombinant Fusion Proteins / metabolism Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization Substrate Specificity |
| Chemical | |
Reg. No./Substance:
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0/ANP32B protein, human; 0/Acetophenones; 0/Antineoplastic Agents; 0/Benzopyrans; 0/Cysteine Proteinase Inhibitors; 0/NSC606985; 0/Neoplasm Proteins; 0/Nuclear Proteins; 0/RNA, Small Interfering; 0/Recombinant Fusion Proteins; 7689-03-4/Camptothecin; 82-08-6/rottlerin; EC 3.4.22.-/CASP3 protein, human; EC 3.4.22.-/Caspase 3 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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