TY - JOUR
T1 - Dok1 and dok2 proteins regulate cell cycle in hematopoietic stem and progenitor cells
AU - Coppin, Emilie
AU - De Grandis, Maria
AU - Pandolfi, Pier Paolo
AU - Arcangeli, Marie Laure
AU - Aurrand-Lions, Michel
AU - Nunès, Jacques A.
N1 - Publisher Copyright:
Copyright © 2016 by The American Association of Immunologists, Inc.
PY - 2016/5/15
Y1 - 2016/5/15
N2 - Dok1 and Dok2 proteins play a crucial role in myeloid cell proliferation as demonstrated by Dok1 and Dok2 gene inactivation, which induces a myeloproliferative disease in aging mice. In this study, we show that Dok1/Dok2 deficiency affects myeloproliferation even at a young age. An increase in the cellularity of multipotent progenitors is observed in young Dok1/Dok2-deficient mice. This is associated with an increase in the cells undergoing cell cycle, which is restricted to myeloid committed progenitors. Furthermore, cellular stress triggered by 5-fluorouracil (5-FU) treatment potentiates the effects of the loss of Dok proteins on multipotent progenitor cell cycle. In addition, Dok1/Dok2 deficiency induces resistance to 5-FU-induced hematopoietic stem cell exhaustion. Taken together, these results demonstrate that Dok1 and Dok2 proteins are involved in the control of hematopoietic stem cell cycle regulation.
AB - Dok1 and Dok2 proteins play a crucial role in myeloid cell proliferation as demonstrated by Dok1 and Dok2 gene inactivation, which induces a myeloproliferative disease in aging mice. In this study, we show that Dok1/Dok2 deficiency affects myeloproliferation even at a young age. An increase in the cellularity of multipotent progenitors is observed in young Dok1/Dok2-deficient mice. This is associated with an increase in the cells undergoing cell cycle, which is restricted to myeloid committed progenitors. Furthermore, cellular stress triggered by 5-fluorouracil (5-FU) treatment potentiates the effects of the loss of Dok proteins on multipotent progenitor cell cycle. In addition, Dok1/Dok2 deficiency induces resistance to 5-FU-induced hematopoietic stem cell exhaustion. Taken together, these results demonstrate that Dok1 and Dok2 proteins are involved in the control of hematopoietic stem cell cycle regulation.
UR - http://www.scopus.com/inward/record.url?scp=84975045587&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.1501037
DO - 10.4049/jimmunol.1501037
M3 - Article
C2 - 27183638
AN - SCOPUS:84975045587
SN - 0022-1767
VL - 196
SP - 4110
EP - 4121
JO - Journal of Immunology
JF - Journal of Immunology
IS - 10
ER -