Intranuclear 3′-phosphoinositide metabolism and Akt signaling: New mechanisms for tumorigenesis and protection against apoptosis?

Alberto M. Martelli, Irene Faenza, Anna Maria Billi, Lucia Manzoli, Camilla Evangelisti, Federica Falà, Lucio Cocco

Research output: Contribution to journalArticlepeer-review

Abstract

Lipid second messengers, particularly those derived from the polyphosphoinositide metabolism, play a pivotal role in multiple cell signaling networks. Phosphoinositide 3-kinase (PI3K) generate 3′-phosphorylated inositol lipids that are key players in a multitude of cell functions. One of the best characterized targets of PI3K lipid products is the serine/threonine protein kinase Akt (protein kinase B, PKB). Recent findings have implicated the PI3K/Akt pathway in tumorigenesis because it stimulates cell proliferation and suppresses apoptosis. However, it was thought that this signal transduction network would exert its carcinogenetic effects mainly by operating in the cytoplasm. Evidence accumulated over the past 15 years has highlighted the presence of an autonomous nuclear inositol lipid cycle, and strongly suggests that lipid molecules are important components of signaling pathways operating at the nuclear level. PI3K, its lipid product phosphatidylinositol (3,4,5) trisphosphate (PtdIns(3,4,5)P3), and Akt have been identified within the nucleus and recent data suggest that they counteract apoptosis also by operating in this cell compartment through a block of caspase-activated DNase and inhibition of chromatin condensation. In this review, we shall summarize the most updated and intriguing findings about nuclear PI3K/PtdIns(3,4,5)P3/Akt in relationship with tumorigenesis and suppression of apoptotic stimuli.

Original languageEnglish
Pages (from-to)1101-1107
Number of pages7
JournalCellular Signalling
Volume18
Issue number8
DOIs
Publication statusPublished - Aug 2006

Keywords

  • Akt
  • Apoptosis
  • Cancer
  • Cardiovascular disorders
  • Nucleus
  • PI3K
  • PtdIns(3,4,5)P

ASJC Scopus subject areas

  • Cell Biology

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