First Author | Silió V | Year | 2012 |
Journal | Mol Biol Cell | Volume | 23 |
Issue | 23 | Pages | 4526-42 |
PubMed ID | 23051731 | Mgi Jnum | J:200258 |
Mgi Id | MGI:5507938 | Doi | 10.1091/mbc.E12-05-0371 |
Citation | Silio V, et al. (2012) Phosphoinositide 3-kinase beta regulates chromosome segregation in mitosis. Mol Biol Cell 23(23):4526-42 |
abstractText | 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, p110alpha and p110beta. Whereas p110alpha is activated at G1-phase entry and promotes protein synthesis and gene expression, p110beta 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 p110alpha and p110beta function in mitosis. p110alpha was activated at mitosis entry and regulated early mitotic events, such as PIP(3) generation, prometaphase progression, and spindle orientation. In contrast, p110beta 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 p110beta function in preserving genomic stability during mitosis. |