Nuclear but not cytosolic phosphoinositide 3-kinase beta has an essential function in cell survival.
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Kumar A, Redondo-Munoz J, Perez-Garcia V, Cortes I, Chagoyen M, Carrera AC
Nuclear but not cytosolic phosphoinositide 3-kinase beta has an essential function in cell survival.
Mol Cell Biol. 2011 May;31(10):2122-33. doi: 10.1128/MCB.01313-10. Epub 2011 Mar 7.
- PubMed ID
- 21383062 [ View in PubMed]
- Abstract
Class I(A) phosphoinositide 3-kinases (PI3Ks) are heterodimeric enzymes composed of a p85 regulatory and a p110 catalytic subunit that induce the formation of 3-polyphosphoinositides, which mediate cell survival, division, and migration. There are two ubiquitous PI3K isoforms p110alpha and p110beta that have nonredundant functions in embryonic development and cell division. However, whereas p110alpha concentrates in the cytoplasm, p110beta localizes to the nucleus and modulates nuclear processes such as DNA replication and repair. At present, the structural features that determine p110beta nuclear localization remain unknown. We describe here that association with the p85beta regulatory subunit controls p110beta nuclear localization. We identified a nuclear localization signal (NLS) in p110beta C2 domain that mediates its nuclear entry, as well as a nuclear export sequence (NES) in p85beta. Deletion of p110beta induced apoptosis, and complementation with the cytoplasmic C2-NLS p110beta mutant was unable to restore cell survival. These studies show that p110beta NLS and p85beta NES regulate p85beta/p110beta nuclear localization, supporting the idea that nuclear, but not cytoplasmic, p110beta controls cell survival.