| Linking sister chromatid cohesion and apoptosis: role of Rad21. | |
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MedLine Citation:
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PMID: 12417729 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Rad21 is one of the major cohesin subunits that holds sister chromatids together until anaphase, when proteolytic cleavage by separase, a caspase-like enzyme, allows chromosomal separation. We show that cleavage of human Rad21 (hRad21) also occurs during apoptosis induced by diverse stimuli. Induction of apoptosis in multiple human cell lines results in the early (4 h after insult) generation of 64- and 60-kDa carboxy-terminal hRad21 cleavage products. We biochemically mapped an apoptotic cleavage site at residue Asp-279 (D(279)) of hRad21. This apoptotic cleavage site is distinct from previously described mitotic cleavage sites. hRad21 is a nuclear protein; however, the cleaved 64-kDa carboxy-terminal product is translocated to the cytoplasm early in apoptosis before chromatin condensation and nuclear fragmentation. Overexpression of the 64-kDa cleavage product results in apoptosis in Molt4, MCF-7, and 293T cells, as determined by TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling) and Annexin V staining, assaying of caspase-3 activity, and examination of nuclear morphology. Given the role of hRad21 in chromosome cohesion, the cleaved C-terminal product and its translocation to the cytoplasm may act as a nuclear signal for apoptosis. In summary, we show that cleavage of a cohesion protein and translocation of the C-terminal cleavage product to the cytoplasm are early events in the apoptotic pathway and cause amplification of the cell death signal in a positive-feedback manner. |
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Authors:
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Debananda Pati; Nenggang Zhang; Sharon E Plon |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, Non-P.H.S. |
Journal Detail:
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Title: Molecular and cellular biology Volume: 22 ISSN: 0270-7306 ISO Abbreviation: Mol. Cell. Biol. Publication Date: 2002 Dec |
Date Detail:
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Created Date: 2002-11-05 Completed Date: 2003-01-02 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 8109087 Medline TA: Mol Cell Biol Country: United States |
Other Details:
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Languages: eng Pagination: 8267-77 Citation Subset: IM |
Affiliation:
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Texas Children's Cancer Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, USA. pati@bcm.tmc.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Sequence Animals Apoptosis / genetics* Caspases / antagonists & inhibitors, metabolism Cells, Cultured Chromatids / metabolism* DNA Repair Enzyme Inhibitors / metabolism Etoposide / metabolism Fungal Proteins / metabolism* Humans In Situ Nick-End Labeling Mitosis / physiology Molecular Sequence Data Mutagenesis, Site-Directed Nuclear Proteins / metabolism* Nucleic Acid Synthesis Inhibitors / metabolism Peptides / metabolism Phosphoproteins / metabolism* Prostaglandins / metabolism Sequence Alignment Tumor Suppressor Protein p53 / metabolism |
| Chemical | |
Reg. No./Substance:
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0/Enzyme Inhibitors; 0/Fungal Proteins; 0/Nuclear Proteins; 0/Nucleic Acid Synthesis Inhibitors; 0/Peptides; 0/Phosphoproteins; 0/Prostaglandins; 0/RAD21 protein, human; 0/Tumor Suppressor Protein p53; 33419-42-0/Etoposide; EC 3.4.22.-/Caspases |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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