| Codanin-1, the protein encoded by the gene mutated in congenital dyserythropoietic anemia type I (CDAN1), is cell cycle-regulated. | |
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MedLine Citation:
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PMID: 19336738 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Congenital dyserythropoietic anemia type I is an inherited autosomal recessive macrocytic anemia associated with ineffective erythropoiesis and the development of secondary hemochromatosis. Distinct erythroid precursors with internuclear chromatin bridges and spongy heterochromatin are pathognomonic for the disease. The mutated gene (CDAN1) encodes a ubiquitously expressed protein of unknown function, codanin-1. Based on the morphological features of congenital dyserythropoietic anemia type I erythroblasts and data on a role in cell cycle progression of codanin-1 homolog in Drosophila we investigated the cellular localization and possible involvement of codanin-1 during the cell cycle. DESIGN AND METHODS: Codanin-1 localization was studied by immunofluorescence and immune electron microscopy. Cell cycle expression of codanin-1 was evaluated using synchronized HeLa cells. E2F proteins are the main regulator of G(1)/S transition. An E2F1-inducible cell line (U20S-ER-E2F1) enabled us to study codanin-1 expression following ectopic E2F1 induction. Direct binding of E2F1 to codanin-1 promoter was assessed by chromatin immunoprecipitation. We used a luciferase-reporter plasmid to study activation of CDAN1 transcription by E2F1. RESULTS: We localized codanin-1 to heterochromatin in interphase cells. During the cell cycle, high levels of codanin-1 were observed in the S phase. At mitosis, codanin-1 underwent phosphorylation, which coincided with its exclusion from condensed chromosomes. The proximal CDAN1 gene promoter region, containing five putative E2F binding sites, was found to be a direct target of E2F1. CONCLUSIONS: Taken together, these data suggest that codanin-1 is a cell cycle-regulated protein active in the S phase. The exact role of codanin-1 during the S phase remains to be determined. Nevertheless this represents the first step towards understanding the function of the proteins involved in congenital dyserythropoietic anemia. |
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Authors:
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Sharon Noy-Lotan; Orly Dgany; Roxane Lahmi; Nathaly Marcoux; Tanya Krasnov; Nissan Yissachar; Doron Ginsberg; Benny Motro; Peretz Resnitzky; Isaac Yaniv; Gary M Kupfer; Hannah Tamary |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-03-31 |
Journal Detail:
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Title: Haematologica Volume: 94 ISSN: 1592-8721 ISO Abbreviation: Haematologica Publication Date: 2009 May |
Date Detail:
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Created Date: 2009-05-01 Completed Date: 2009-09-25 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 0417435 Medline TA: Haematologica Country: Italy |
Other Details:
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Languages: eng Pagination: 629-37 Citation Subset: IM |
Affiliation:
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Pediatric Hematology Oncology, Schneider Children's Medical Center of Israel, 14 Kaplan Street, Petah Tiqva 49 202, Israel. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Sequence Anemia, Dyserythropoietic, Congenital / classification, genetics*, pathology Base Sequence Binding Sites / genetics Blotting, Western Cell Cycle / physiology* Cell Division / physiology Cell Line, Tumor Chromatin Immunoprecipitation E2F1 Transcription Factor / genetics, metabolism G2 Phase / physiology Gene Expression / drug effects Glycoproteins / genetics*, metabolism Hela Cells Heterochromatin / metabolism, ultrastructure Humans Leupeptins / pharmacology Luciferases / genetics, metabolism Microscopy, Confocal Microscopy, Immunoelectron Molecular Sequence Data Mutation* Phosphorylation Protein Binding Tamoxifen / analogs & derivatives, pharmacology |
| Chemical | |
Reg. No./Substance:
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0/CDAN1 protein, human; 0/E2F1 Transcription Factor; 0/E2F1 protein, human; 0/Glycoproteins; 0/Heterochromatin; 0/Leupeptins; 10540-29-1/Tamoxifen; 133407-82-6/benzyloxycarbonylleucyl-leucyl-leucine aldehyde; 68392-35-8/4-hydroxytamoxifen; EC 1.13.12.-/Luciferases |
| Comments/Corrections | |
Comment In:
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Haematologica. 2009 May;94(5):599-602
[PMID:
19407313
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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