D-Cyclins Repress Apoptosis in Hematopoietic Cells by Controlling Death Receptor Fas and Its Ligand FasL
D-type cyclins (D1, D2, and D3) are components of the mammalian core cell-cycle machinery and function to drive cell proliferation. Here, we report that D-cyclins perform a rate-limiting antiapoptotic function in vivo. We found that acute shutdown of all three D-cyclins in bone marrow of adult mice...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Elsevier
2017
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| Online Access: | http://hdl.handle.net/1721.1/106321 https://orcid.org/0000-0001-8855-8647 |
| _version_ | 1811090362573258752 |
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| author | Choi, Yoon Jong Saez, Borja Anders, Lars Hydbring, Per Stefano, Joanna Bacon, Nickolas A. Cook, Colleen Kalaszczynska, Ilona Signoretti, Sabina Scadden, David T. Sicinski, Piotr Young, Richard A. |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Choi, Yoon Jong Saez, Borja Anders, Lars Hydbring, Per Stefano, Joanna Bacon, Nickolas A. Cook, Colleen Kalaszczynska, Ilona Signoretti, Sabina Scadden, David T. Sicinski, Piotr Young, Richard A. |
| author_sort | Choi, Yoon Jong |
| collection | MIT |
| description | D-type cyclins (D1, D2, and D3) are components of the mammalian core cell-cycle machinery and function to drive cell proliferation. Here, we report that D-cyclins perform a rate-limiting antiapoptotic function in vivo. We found that acute shutdown of all three D-cyclins in bone marrow of adult mice resulted in massive apoptosis of all hematopoietic cell types. We demonstrate that adult hematopoietic stem cells are particularly dependent on D-cyclins for survival and that they are especially sensitive to cyclin D loss. Surprisingly, we found that the antiapoptotic function of D-cyclins also operates in quiescent hematopoietic stem and progenitor cells. Our analyses revealed that D-cyclins repress the expression of the death receptor Fas and its ligand, FasL. Acute ablation of D-cyclins upregulated these proapoptotic genes and led to Fas- and caspase 8-dependent apoptosis. These results reveal an unexpected function of cell-cycle proteins in controlling apoptosis in normal cell homeostasis. |
| first_indexed | 2024-09-23T14:44:23Z |
| format | Article |
| id | mit-1721.1/106321 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T14:44:23Z |
| publishDate | 2017 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/1063212022-09-29T10:15:31Z D-Cyclins Repress Apoptosis in Hematopoietic Cells by Controlling Death Receptor Fas and Its Ligand FasL Choi, Yoon Jong Saez, Borja Anders, Lars Hydbring, Per Stefano, Joanna Bacon, Nickolas A. Cook, Colleen Kalaszczynska, Ilona Signoretti, Sabina Scadden, David T. Sicinski, Piotr Young, Richard A. Massachusetts Institute of Technology. Department of Biology Young, Richard A D-type cyclins (D1, D2, and D3) are components of the mammalian core cell-cycle machinery and function to drive cell proliferation. Here, we report that D-cyclins perform a rate-limiting antiapoptotic function in vivo. We found that acute shutdown of all three D-cyclins in bone marrow of adult mice resulted in massive apoptosis of all hematopoietic cell types. We demonstrate that adult hematopoietic stem cells are particularly dependent on D-cyclins for survival and that they are especially sensitive to cyclin D loss. Surprisingly, we found that the antiapoptotic function of D-cyclins also operates in quiescent hematopoietic stem and progenitor cells. Our analyses revealed that D-cyclins repress the expression of the death receptor Fas and its ligand, FasL. Acute ablation of D-cyclins upregulated these proapoptotic genes and led to Fas- and caspase 8-dependent apoptosis. These results reveal an unexpected function of cell-cycle proteins in controlling apoptosis in normal cell homeostasis. 2017-01-10T15:53:02Z 2017-01-10T15:53:02Z 2014-06 2014-03 Article http://purl.org/eprint/type/JournalArticle 1534-5807 1878-1551 http://hdl.handle.net/1721.1/106321 Choi, Yoon Jong et al. “D-Cyclins Repress Apoptosis in Hematopoietic Cells by Controlling Death Receptor Fas and Its Ligand FasL.” Developmental Cell 30.3 (2014): 255–267. https://orcid.org/0000-0001-8855-8647 en_US http://dx.doi.org/10.1016/j.devcel.2014.06.015 Developmental Cell Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier PMC |
| spellingShingle | Choi, Yoon Jong Saez, Borja Anders, Lars Hydbring, Per Stefano, Joanna Bacon, Nickolas A. Cook, Colleen Kalaszczynska, Ilona Signoretti, Sabina Scadden, David T. Sicinski, Piotr Young, Richard A. D-Cyclins Repress Apoptosis in Hematopoietic Cells by Controlling Death Receptor Fas and Its Ligand FasL |
| title | D-Cyclins Repress Apoptosis in Hematopoietic Cells by Controlling Death Receptor Fas and Its Ligand FasL |
| title_full | D-Cyclins Repress Apoptosis in Hematopoietic Cells by Controlling Death Receptor Fas and Its Ligand FasL |
| title_fullStr | D-Cyclins Repress Apoptosis in Hematopoietic Cells by Controlling Death Receptor Fas and Its Ligand FasL |
| title_full_unstemmed | D-Cyclins Repress Apoptosis in Hematopoietic Cells by Controlling Death Receptor Fas and Its Ligand FasL |
| title_short | D-Cyclins Repress Apoptosis in Hematopoietic Cells by Controlling Death Receptor Fas and Its Ligand FasL |
| title_sort | d cyclins repress apoptosis in hematopoietic cells by controlling death receptor fas and its ligand fasl |
| url | http://hdl.handle.net/1721.1/106321 https://orcid.org/0000-0001-8855-8647 |
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