| Proteolytic processing of cut homeobox 1 by neutrophil elastase in the MV4;11 myeloid leukemia cell line. | |
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MedLine Citation:
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PMID: 18403643 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Proteolytic processing by cathepsin L generates p110 Cut homeobox 1 (CUX1) at the end of the G(1) phase, whereas an alternative transcript encodes p75 CUX1. These short CUX1 isoforms were reported to be overexpressed in cancer cells, and transgenic mice overexpressing the p75 isoform were found to develop myeloproliferative disease-like myeloid leukemias. In the present study, we report that the neutrophil elastase can also generate a short CUX1 isoform in the MV4;11 acute myeloid leukemia cell line. Proteolytic processing was so efficient that the full-length CUX1 protein was detected only when cells were maintained in the presence of the specific elastase inhibitor III. In agreement with these findings, higher levels of the processed cyclin E isoforms were also detected in MV4;11 cells. Reappearance of full-length cyclin E and CUX1 could be induced upon the treatment of MV4;11 cells with the differentiation inducer phorbol 12-myristate 13-acetate or, unexpectedly, following overexpression of a short recombinant CUX1 protein. In both cases, the mechanism involved transcriptional repression of the neutrophil elastase gene. This result revealed a negative feedback loop whereby CUX1 shuts down the expression of the protease that cleaves it. Overall, the findings in MV4;11 and other cancer cells suggest that various mechanisms are used in cancer to favor the expression of short CUX1 isoforms. |
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Authors:
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Brigitte Goulet; Yelena Markovic; Lam Leduy; Alain Nepveu |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Molecular cancer research : MCR Volume: 6 ISSN: 1541-7786 ISO Abbreviation: Mol. Cancer Res. Publication Date: 2008 Apr |
Date Detail:
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Created Date: 2008-04-11 Completed Date: 2008-07-07 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101150042 Medline TA: Mol Cancer Res Country: United States |
Other Details:
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Languages: eng Pagination: 644-53 Citation Subset: IM |
Affiliation:
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Molecular Oncology Group, McGill University Health Center, Montreal, Quebec, Canada H3A 1A1. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Cell Extracts Cell Line, Tumor Cell Nucleus / drug effects, metabolism Cell Proliferation / drug effects Cyclin E / metabolism Gene Expression Regulation, Neoplastic / drug effects Homeodomain Proteins / chemistry, metabolism* Humans Leukemia, Myeloid / enzymology*, pathology Leukocyte Elastase / antagonists & inhibitors, genetics, metabolism* Protein Processing, Post-Translational* / drug effects Recombinant Proteins / metabolism Serine Proteinase Inhibitors / pharmacology Tetradecanoylphorbol Acetate / pharmacology |
| Chemical | |
Reg. No./Substance:
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0/Cell Extracts; 0/Cyclin E; 0/Homeodomain Proteins; 0/Recombinant Proteins; 0/Serine Proteinase Inhibitors; 16561-29-8/Tetradecanoylphorbol Acetate; EC 3.4.21.37/Leukocyte Elastase |
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