| PU.1, a novel caspase-3 substrate, partially contributes to chemotherapeutic agents-induced apoptosis in leukemic cells. | |
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MedLine Citation:
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PMID: 19281794 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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PU.1 is one of key regulators of hematopoietic cell development, a tightly-regulated lineage-specific process. Here we provide the first evidence that PU.1 protein is cleaved into two fragments of 24 kDa and 16 kDa during apoptosis progression in leukemic cell lines and primary leukemic cells. Further experiments with specific capase-3 inhibitor Z-DEVD-fmk and the in vitro proteolytic system confirmed that PU.1 is a direct target of caspase-3. Using site-directed mutagenesis analyses, the aspartic acid residues at positions 97 and 151 of PU.1 protein were identified as capsase-3 target sites. More intriguingly, the suppression of PU.1 expression by small interfering RNAs (siRNAs) significantly inhibits DNA-damaging agents NSC606985 and etoposide-induced apoptosis in leukemic cells, together with the up-regulated expression of anti-apoptotic bcl-2 gene. These results would provide new insights for understanding the mechanism of PU.1 protein in hematopoiesis and leukemogenesis. |
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Authors:
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Meng Zhao; Xu-Fang Duan; Dong-Hua Wen; Guo-Qiang Chen |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-03-10 |
Journal Detail:
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Title: Biochemical and biophysical research communications Volume: 382 ISSN: 1090-2104 ISO Abbreviation: Biochem. Biophys. Res. Commun. Publication Date: 2009 May |
Date Detail:
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Created Date: 2009-04-15 Completed Date: 2009-05-15 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0372516 Medline TA: Biochem Biophys Res Commun Country: United States |
Other Details:
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Languages: eng Pagination: 508-13 Citation Subset: IM |
Affiliation:
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Institute of Health Sciences, Shanghai Institutes for Biological Sciences of Chinese Academy of Sciences & Shanghai Jiao-Tong University School of Medicine, Luwan, Shanghai 200025, China. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Antineoplastic Agents
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pharmacology Apoptosis* / genetics Aspartic Acid / genetics, metabolism Camptothecin / analogs & derivatives, pharmacology Caspase 3 / antagonists & inhibitors, metabolism* Cell Line, Tumor Cysteine Proteinase Inhibitors / pharmacology Etoposide / pharmacology Humans Leukemia / drug therapy*, enzymology, pathology Mutagenesis, Site-Directed Oligopeptides / pharmacology Proto-Oncogene Proteins / genetics, physiology* Proto-Oncogene Proteins c-bcl-2 / metabolism RNA, Small Interfering / genetics Trans-Activators / genetics, physiology* |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents; 0/Cysteine Proteinase Inhibitors; 0/NSC606985; 0/Oligopeptides; 0/Proto-Oncogene Proteins; 0/Proto-Oncogene Proteins c-bcl-2; 0/RNA, Small Interfering; 0/Trans-Activators; 0/benzoylcarbonyl-aspartyl-glutamyl-valyl-aspartyl-fluoromethyl ketone; 0/proto-oncogene protein Spi-1; 33419-42-0/Etoposide; 56-84-8/Aspartic Acid; 7689-03-4/Camptothecin; EC 3.4.22.-/Caspase 3 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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