Phosphoinositide 3-kinase β regulates chromosome segregation in mitosis.
Class I(A) phosphoinositide 3-kinases (PI3K) are enzymes composed of a p85 regulatory and a p110 catalytic subunit that control formation of 3-poly-phosphoinositides (PIP(3)). The PI3K pathway regulates cell survival, migration, and division, and is mutated in approximately half of human tumors. For this reason, it is important to define the function of the ubiquitous PI3K subunits, p110α and p110β. Whereas p110α is activated at G1-phase entry and promotes protein synthesis and gene expression, p110β activity peaks in S phase and regulates DNA synthesis. PI3K activity also increases at the onset of mitosis, but the isoform activated is unknown; we have examined p110α and p110β function in mitosis. p110α was activated at mitosis entry and regulated early mitotic events, such as PIP(3) generation, prometaphase progression, and spindle orientation. In contrast, p110β was activated near metaphase and controlled dynein/dynactin and Aurora B activities in kinetochores, chromosome segregation, and optimal function of the spindle checkpoint. These results reveal a p110β function in preserving genomic stability during mitosis.
Department of Immunology and Oncology, Centro Nacional de Biotecnología/CSIC, Campus Universidad Autónoma de Madrid, Cantoblanco, Madrid E-28049, Spain.
Virginia
V
Silió
Javier
J
Redondo-Muñoz
Ana C
AC
Carrera
D000818:Animals; D064107:Aurora Kinase B; D064127:Aurora Kinases; D002453:Cell Cycle; D002470:Cell Survival; D020090:Chromosome Segregation; D058543:Class Ia Phosphatidylinositol 3-Kinase / Q000235:genetics / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis / Q000235:genetics; D004398:Dyneins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D018386:Kinetochores / Q000378:metabolism; D051379:Mice; D008938:Mitosis; D041681:NIH 3T3 Cells; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D015398:Signal Transduction; D008941:Spindle Apparatus / Q000235:genetics
D064107:Aurora Kinase B; D064127:Aurora Kinases; D058543:Class Ia Phosphatidylinositol 3-Kinase; D004247:DNA; D004398:Dyneins; D019869:Phosphatidylinositol 3-Kinases; D020033:Protein Isoforms; D017346:Protein Serine-Threonine Kinases; C576921:AURKB protein, human; C576924:Aurkb protein, mouse