Nuclear phosphoinositides and their roles in cell biology and disease

Alberto M. Martelli, Andrea Ognibene, Francesca Buontempo, Milena Fini, Daniela Bressanin, Kaoru Goto, James A. McCubrey, Lucio Cocco, Camilla Evangelisti

Research output: Contribution to journalArticle

Abstract

Since the late 1980s, a growing body of evidence has documented that phosphoinositides and their metabolizing enzymes, which regulate a large variety of cellular functions both in the cytoplasm and at the plasma membrane, are present also within the nucleus, where they are involved in processes such as cell proliferation, differentiation, and survival. Remarkably, nuclear phosphoinositide metabolism operates independently from that present elsewhere in the cell. Although nuclear phosphoinositides generate second messengers such as diacylglycerol and inositol 1,4,5 trisphosphate, it is becoming increasingly clear that they may act by themselves to influence chromatin structure, gene expression, DNA repair, and mRNA export. The understanding of the biological roles played by phosphoinositides is supported by the recent acquisitions demonstrating the presence in the nuclear compartment of several proteins harboring phosphoinositide-binding domains. Some of these proteins have functional roles in RNA splicing/processing and chromatin assembly. Moreover, recent evidence shows that nuclear phospholipase Cβ1 (a key phosphoinositide metabolizing enzyme) could somehow be involved in the myelodysplastic syndrome, i.e. a hematopoietic disorder that frequently evolves into an acute leukemia. This review aims to highlight the most significant and updated findings about phosphoinositide metabolism in the nucleus under both physiological and pathological conditions.

Original languageEnglish
Pages (from-to)436-457
Number of pages22
JournalCritical Reviews in Biochemistry and Molecular Biology
Volume46
Issue number5
DOIs
Publication statusPublished - Oct 2011

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Keywords

  • Gene expression
  • Myelodysplastic syndrome
  • Myogenic differentiation
  • Phospholipase C
  • Proliferation
  • Signal transduction

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry

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