Por favor, use este identificador para citar o enlazar este Item:http://hdl.handle.net/20.500.12105/10673
Título
Functional reprogramming of polyploidization in megakaryocytes.
Autor(es)
Trakala, Marianna CNIO | Rodríguez-Acebes, Sara | Maroto, María | Symonds, Catherine E | Santamaria, David CNIO | Malumbres, Marcos | Ortega Jimenez, Sagrario CNIO | Barbacid, Mariano CNIO | Mendez, Juan CNIO | Malumbres Martinez, Marcos CNIO
Fecha de publicación
2015-01-26
Cita
Dev Cell . 2015;32(2):155-67.
Idioma
Inglés
Tipo de documento
journal article
Resumen
Polyploidization is a natural process that frequently accompanies differentiation; its deregulation is linked to genomic instability and cancer. Despite its relevance, why cells select different polyploidization mechanisms is unknown. Here we report a systematic genetic analysis of endomitosis, a process in which megakaryocytes become polyploid by entering mitosis but aborting anaphase. Whereas ablation of the APC/C cofactor Cdc20 results in mitotic arrest and severe thrombocytopenia, lack of the kinases Aurora-B, Cdk1, or Cdk2 does not affect megakaryocyte polyploidization or platelet levels. Ablation of Cdk1 forces a switch to endocycles without mitosis, whereas polyploidization in the absence of Cdk1 and Cdk2 occurs in the presence of aberrant re-replication events. Importantly, ablation of these kinases rescues the defects in Cdc20 null megakaryocytes. These findings suggest that endomitosis can be functionally replaced by alternative polyploidization mechanisms in vivo and provide the cellular basis for therapeutic approaches aimed to discriminate mitotic and polyploid cells.
Palabras clave
CYCLIN-DEPENDENT KINASES | ENDOMITOTIC CELL-CYCLE | S-PHASE | RE-REPLICATION | AURORA B | GENE AMPLIFICATION; | GENOMIC STABILITY | MITOTIC EXIT; | IN-VIVO; | CDK1
MESH
Polyploidy | Anaphase | Animals | Cdc20 Proteins | Cells, Cultured | Megakaryocytes | Mice | Mitosis | Protein-Serine-Threonine Kinases
Versión en línea
DOI
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