科研之友
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摘要
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 p110 alpha and p110 beta that have nonredundant functions in embryonic development and cell division. However, whereas p110 alpha concentrates in the cytoplasm, p110 beta localizes to the nucleus and modulates nuclear processes such as DNA replication and repair. At present, the structural features that determine p110 beta nuclear localization remain unknown. We describe here that association with the p85 beta regulatory subunit controls p110 beta nuclear localization. We identified a nuclear localization signal (NLS) in p110 beta C2 domain that mediates its nuclear entry, as well as a nuclear export sequence (NES) in p85 beta. Deletion of p110 beta induced apoptosis, and complementation with the cytoplasmic C2-NLS p110 beta mutant was unable to restore cell survival. These studies show that p110 beta NLS and p85 beta NES regulate p85 beta/p110 beta nuclear localization, supporting the idea that nuclear, but not cytoplasmic, p110 beta controls cell survival.
- 出版日期2011-5
