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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Yamak, Abir Latinkic, Branko V. Nemer, Mona Dali, Rola Temsah, Rana |
| Description | Author Affiliation: Yamak A ( Laboratory of Cardiac Development and Differentiation, Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, ON, Canada, K1N 6N5.); |
| Abstract | The G1 cyclins play a pivotal role in regulation of cell differentiation and proliferation. The mechanisms underlying their cell-specific roles are incompletely understood. Here, we show that a G1 cyclin, cyclin D2 (CycD2), enhances the activity of transcription factor GATA4, a key regulator of cardiomyocyte growth and differentiation. GATA4 recruits CycD2 to its target promoters, and their interaction results in synergistic activation of GATA-dependent transcription. This effect is specific to CycD2 because CycD1 is unable to potentiate activity of GATA4 and is CDK-independent. GATA4 physically interacts with CycD2 through a discreet N-terminal activation domain that is essential for the cardiogenic activity of GATA4. Human mutations in this domain that are linked to congenital heart disease interfere with CycD2-GATA4 synergy. Cardiogenesis assays in Xenopus embryos indicate that CycD2 enhances the cardiogenic function of GATA4. Together, our data uncover a role for CycD2 as a cardiogenic coactivator of GATA4 and suggest a paradigm for cell-specific effects of cyclin Ds. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 4 |
| Volume Number | 111 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2014-01-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Cyclin D2 Physiology GATA4 Transcription Factor Heart Embryology Organogenesis Amino Acid Sequence Animals Chemistry Molecular Sequence Data Sequence Homology, Amino Acid Trans-Activators Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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