D-Cyclins Repress Apoptosis in Hematopoietic Cells by Controlling Death Receptor Fas and Its Ligand FasL
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.; Sicinski, Piotr; Young, Richard A; ... Show more Show less
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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.
DepartmentMassachusetts Institute of Technology. Department of Biology
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.
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