Phosphoinositide 3-kinase ? regulates chromosome segregation in mitosis.

ABSTRACT: 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, p110? and p110?. Whereas p110? is activated at G1-phase entry and promotes protein synthesis and gene expression, p110? 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 p110? and p110? function in mitosis. p110? was activated at mitosis entry and regulated early mitotic events, such as PIP(3) generation, prometaphase progression, and spindle orientation. In contrast, p110? 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 p110? function in preserving genomic stability during mitosis.

SUBMITTER: Silio V 

PROVIDER: S-EPMC3510015 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature