RT Journal Article
T1 Activation of the endomitotic spindle assembly checkpoint and thrombocytopenia in Plk1-deficient mice
A1 Trakala, Marianna
A1 Partida, David
A1 Salazar Roa, María
A1 Maroto, María
A1 Wachowicz, Paulina
A1 Carcer, Guillermo de
A1 Malumbres, Marcos
AB Polyploidization in megakaryocytes is achieved by endomitosis, a specialized cell cycle in which DNA replication is followed by aberrant mitosis. Typical mitotic regulators such as Aurora kinases or Cdk1 are dispensable for megakaryocyte maturation, and inhibition of mitotic kinases may in fact promote megakaryocyte maturation. However, we show here that Polo-like kinase 1 (Plk1) is required for endomitosis, and ablation of the Plk1 gene in megakaryocytes results in defective polyploidization accompanied by mitotic arrest and cell death. Lack of Plk1 results in defective centrosome maturation and aberrant spindle pole formation, thus impairing the formation of multiple poles typically found in megakaryocytes. In these conditions, megakaryocytes arrest for a long time in mitosis and frequently die. Mitotic arrest in wild-type megakaryocytes treated with Plk1 inhibitors or Plk1-null cells is triggered by the spindle assembly checkpoint (SAC), and can be rescued in the presence of SAC inhibitors. These data suggest that, despite the dispensability of proper chromosome segregation in megakaryocytes, an endomitotic SAC is activated in these cells upon Plk1 inhibition. SAC activation results in defective maturation of megakaryocytes and cell death, thus raising a note of caution in the use of Plk1 inhibitors in therapeutic strategies based on polyploidization regulators.
PB The American Society of Hematology
SN 0006-4971
YR 2015
FD 2015
LK https://hdl.handle.net/20.500.14352/97346
UL https://hdl.handle.net/20.500.14352/97346
LA eng
NO Marianna Trakala, David Partida, María Salazar-Roa, María Maroto, Paulina Wachowicz, Guillermo de Cárcer, Marcos Malumbres; Activation of the endomitotic spindle assembly checkpoint and thrombocytopenia in Plk1-deficient mice. Blood 2015; 126 (14): 1707–1714. doi: https://doi.org/10.1182/blood-2015-03-634402
NO Foundación La Caixa
NO Worldwide Cancer Research
NO Comunidad de Madrid
NO Ministerio de Economía y Competitividad (España)
NO European Commission
DS Docta Complutense
RD 8 abr 2025