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rdf:type |
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lifeskim:mentions |
umls-concept:C0013081,
umls-concept:C0205314,
umls-concept:C0291573,
umls-concept:C0439677,
umls-concept:C0679622,
umls-concept:C1326205,
umls-concept:C1332090,
umls-concept:C1517806,
umls-concept:C1710236,
umls-concept:C1879547,
umls-concept:C2349975
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pubmed:issue |
3
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pubmed:dateCreated |
2010-3-5
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pubmed:abstractText |
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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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/ANP32B protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Acetophenones,
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Benzopyrans,
http://linkedlifedata.com/resource/pubmed/chemical/CASP3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Camptothecin,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Cysteine Proteinase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/NSC606985,
http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/rottlerin
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
1460-2180
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:volume |
31
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
419-26
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pubmed:meshHeading |
pubmed-meshheading:20015864-Acetophenones,
pubmed-meshheading:20015864-Antineoplastic Agents,
pubmed-meshheading:20015864-Apoptosis,
pubmed-meshheading:20015864-Benzopyrans,
pubmed-meshheading:20015864-Camptothecin,
pubmed-meshheading:20015864-Carcinoma,
pubmed-meshheading:20015864-Caspase 3,
pubmed-meshheading:20015864-Cell Line, Tumor,
pubmed-meshheading:20015864-Cysteine Proteinase Inhibitors,
pubmed-meshheading:20015864-Down-Regulation,
pubmed-meshheading:20015864-Enzyme Activation,
pubmed-meshheading:20015864-Female,
pubmed-meshheading:20015864-Humans,
pubmed-meshheading:20015864-Leukemia, Myeloid,
pubmed-meshheading:20015864-Male,
pubmed-meshheading:20015864-Neoplasm Proteins,
pubmed-meshheading:20015864-Neoplasms,
pubmed-meshheading:20015864-Nuclear Proteins,
pubmed-meshheading:20015864-RNA, Small Interfering,
pubmed-meshheading:20015864-RNA Interference,
pubmed-meshheading:20015864-Recombinant Fusion Proteins,
pubmed-meshheading:20015864-Spectrometry, Mass, Matrix-Assisted Laser...,
pubmed-meshheading:20015864-Substrate Specificity
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pubmed:year |
2010
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pubmed:articleTitle |
Downregulation of ANP32B, a novel substrate of caspase-3, enhances caspase-3 activation and apoptosis induction in myeloid leukemic cells.
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pubmed:affiliation |
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.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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