| A splice variant of cyclin D2 regulates cardiomyocyte cell cycle through a novel protein aggregation pathway. | |
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MedLine Citation:
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PMID: 19401331 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The mammalian heart lacks intrinsic ability to replace diseased myocardium with newly divided myocytes. There is scant information on mechanisms regulating cell cycle exit in cardiomyocytes. We cloned a splice variant of cyclin D2 (D2SV) from the mouse heart and found a novel role for this protein in cardiomyocyte cell cycle exit. We report that D2SV is highly expressed in embryonic myocardium compared with the adult heart. Localization studies indicate that D2SV is retained in the endoplasmic reticulum (ER), Golgi and lysosomal compartments and subjected to ER-stress-associated protein aggregation. D2SV aggregation relies on the motor activities of dynein and is blocked by ER stress modulators. The ability of D2SV to sequester other cell cycle proteins provides a mechanistic explanation for its effects on cardiomyocyte cell cycle. We show that D2SV-induced cell cycle exit can be rescued by overexpression of D-type and B-type cyclins. We suggest that protein aggregation may be a major block for cardiomyocyte cell cycle reactivation. |
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Authors:
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Qian Sun; Feixiong Zhang; Karim Wafa; Timothy Baptist; Kishore B S Pasumarthi |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-04-28 |
Journal Detail:
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Title: Journal of cell science Volume: 122 ISSN: 0021-9533 ISO Abbreviation: J. Cell. Sci. Publication Date: 2009 May |
Date Detail:
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Created Date: 2009-05-07 Completed Date: 2009-07-09 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 0052457 Medline TA: J Cell Sci Country: England |
Other Details:
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Languages: eng Pagination: 1563-73 Citation Subset: IM |
Affiliation:
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Department of Pharmacology, Sir Charles Tupper Medical Building, Dalhousie University, Halifax, NS, B3H 1X5 Canada. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Alternative Splicing* Amino Acid Sequence Animals Cell Cycle* Cells, Cultured Cloning, Molecular Cyclin B / metabolism Cyclin B1 Cyclin D2 Cyclin-Dependent Kinase 4 / metabolism Cyclins / genetics, metabolism* Cytoskeleton / metabolism Dyneins / metabolism Endoplasmic Reticulum / metabolism Gene Expression Regulation, Developmental Golgi Apparatus / metabolism Heart / embryology Lysosomes / metabolism Mice Molecular Sequence Data Myocytes, Cardiac / metabolism* Protein Binding Protein Isoforms Stress, Physiological Transcription Factor CHOP / metabolism Transfection |
| Chemical | |
Reg. No./Substance:
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0/Ccnb1 protein, mouse; 0/Ccnd2 protein, mouse; 0/Cyclin B; 0/Cyclin B1; 0/Cyclin D2; 0/Cyclins; 0/Protein Isoforms; 147336-12-7/Transcription Factor CHOP; EC 2.7.1.37/Cdk4 protein, mouse; EC 2.7.11.22/Cyclin-Dependent Kinase 4; EC 3.6.4.2/Dyneins |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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