D-Cyclins Repress Apoptosis in Hematopoietic Cells by Controlling Death Receptor Fas and Its Ligand FasL
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Young_D-cyclins.pdf
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Author(s)
Choi, Yoon Jong
Saez, Borja
Anders, Lars
Hydbring, Per
Stefano, Joanna
Bacon, Nickolas A.
Cook, Colleen
Kalaszczynska, Ilona
Signoretti, Sabina
Scadden, David T.
Date Issued
June 2014
Journal
Developmental Cell
Publisher
Elsevier
Citation
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.
Version
Author's final manuscript
Abstract
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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/j.devcel.2014.06.015
