Science's STKE | 17 September 2002

Review Update: Emerging Functions of Nuclear Lipids

Robin F. Irvine*

Department of Pharmacology, University of Cambridge, Cambridge CB2 1QJ, UK.

A reader's guide to the revised STKE Review "Nuclear lipid signaling," http://www.stke.org/cgi/content/full/sigtrans;2002/150/re13


Since the publication of the original review two years ago, there have been many exciting and encouraging advances in our knowledge of nuclear lipid metabolism. These advances, which are discussed in the revised version of the review, include findings that provide new hints to the functions for nuclear lipids and some of the regulatory mechanisms controlling their synthesis and metabolism. The updated review includes an entirely new section called "Other Inositol Lipids," which describes the regulation and potential functions for 3-phosphorylated lipids and other inositol lipids, including phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] and PtdIns5P, that have been detected in the nucleus. In addition, a new figure (Fig. 5 in the updated review) has been included that illustrates the putative functions for the various lipids and indicates some suggested points of regulation. Some highlights of the updated review (with selected reference examples) are listed below, organized by the sections that contain the most details about the topics.

PI-PLC in the Nucleus

  • Nuclear phosphoinositide-specific phospholipase C ß1 (PI-PLCß1) (probably the b splice variant) may be regulated through phosphorylation by extracellular signal-regulated protein kinases (ERKs) (1).

Nuclear Diacylglycerol

  • The nuclear localization of diacylglyerol (DAG) kinases has been found to involve several different isoforms that are regulated in complex ways.

The Cell Cycle and Signaling by Nuclear Lipids

  • Complex changes in the mass levels and metabolism of nuclear inositol lipids occur during the cell cycle (2).
  • New possible functions have been revealed for PtdIns(4,5)P2; for example, it may be involved with premessenger RNA splicing (3).

Other Inositol Lipids

  • New angles on the nuclear metabolism and function of the higher inositol phosphates have emerged, including a possible role for inositol hexakisphosphate in the regulation of DNA repair (4).
  • The presence in the nucleus of 3-phosphorylated inositol lipids and the enzymes that make them has been extended. For example, a complex story is emerging involving PIKE, a nuclear guanosine triphosphatase that activates phosphatidylinositol 3-kinase (5). PIKE, in turn, may be regulated by the Src-homology 3 (SH3) domain of PI-PLC{gamma} (6).
  • Indirect evidence implies a nuclear function for PtdIns(3,4)P2 (7).

Other Lipids

  • A new nuclear function for phosphatidylcholine is suggested by the specific nuclear synthesis of this lipid with a saturated fatty acyl profile (8).


*Contact information. E-mail, rfi20{at}cam.ac.uk


    • A. Xu, P. G. Suh, N. Marmy Conus, R. B. Pearson, O. Y. Seok, L. Cocco, R. S. Gilmour, Phosphorylation of nuclear phospholipase C ß1 by extracellular signal-regulated kinase mediates the mitogenic action of insulin-like growth factor I. Mol. Cell. Biol. 21, 2981-2990 (2001). [Abstract/Full Text]
    • J. H. Clarke, A. J. Letcher, S. D'Santos C, J. R. Halstead, R. F. Irvine, N. Divecha, Inositol lipids are regulated during cell cycle progression in the nuclei of murine erythroleukaemia cells. Biochem. J. 357, 905-910 (2001). [Medline]
    • S. L. Osborne, C. L. Thomas, S. Gschmeissner, G. Schiavo, Nuclear PtdIns(4,5)P2 assembles in a mitotically regulated particle involved in pre-mRNA splicing. J. Cell Sci. 114, 2501-2511 (2001). [Abstract/Full Text]
    • L. A. Hanakahi, M. Bartlet-Jones, C. Chappell, D. Pappin, S. C. West, Binding of inositol phosphate to DNA-PK and stimulation of double-strand break repair. Cell 102, 721-729 (2000). [Medline]
    • K. Ye, K. J. Hurt, F. Y. Wu, M. Fang, H. R. Luo, J. J. Hong, S. Blackshaw, C. D. Ferris, S. H. Snyder, PIKE: A nuclear GTPase that enhances PI3kinase activity and is regulated by protein 4.1N. Cell 103, 919-930 (2000). [Medline]
    • K. Ye, B. Aghdasi, H. R. Luo, J. L. Moriarity, F. Y. Wu, J. J. Hong, K. J. Hurt, S. S. Bae, P. G. Suh, S. H. Snyder, Phospholipase C {gamma}1 is a physiological guanine nucleotide exchange factor for the nuclear GTPase PIKE. Nature 415, 541-544 (2002). [Medline]
    • T. Yokogawa, S. Nagata, Y. Nishio, T. Tsutsumi, S. Ihara, R. Shirai, K. Morita, M. Umeda, Y. Shirai, N. Saitoh, Y. Fukui, Evidence that 3'-phosphorylated polyphosphoinositides are generated at the nuclear surface: use of immunostaining technique with monoclonal antibodies specific for PI 3,4-P2. FEBS Lett. 473, 222-226 (2000). [Medline]
    • A. N. Hunt, G. T. Clark, G. S. Attard, A. D. Postle, Highly saturated endonuclear phosphatidylcholine is synthesized in situ and colocated with CDP-choline pathway enzymes. J. Biol. Chem. 276, 8492-8499 (2001). [Abstract/Full Text]


      Citation: R. Irvine, Review update: Emerging functions of nuclear lipids. Science's STKE (2002), http://stke.sciencemag.org/cgi/content/full/sigtrans;2002/150/re13/DC1. [PDF]

      Citation for the related Review: R. F. Irvine, Nuclear lipid signaling. Science's STKE (2002), http://www.stke.org/cgi/content/full/sigtrans;2002/150/re13. [Abstract] [Full Text]

      Citation for the previous version of this Review: R. Irvine, Nuclear lipid signaling. Science's STKE (2000), http://www.stke.org/cgi/content/full/OC_sigtrans;2000/48/re1. [Abstract] [Full Text]

      © 2002 American Association for the Advancement of Science