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J Biol Chem, Vol. 274, Issue 8, 4890-4899, February 19, 1999

Edible Mushroom (Agaricus bisporus) Lectin, Which Reversibly Inhibits Epithelial Cell Proliferation, Blocks Nuclear Localization Sequence-dependent Nuclear Protein Import

Lu-Gang Yu, David G. Fernig^§, Michael R. H. White^§, David G. Spiller^§, Paul Appleton, Richard C. Evans, Ian Grierson, John A. Smith^§, Helen Davies, Oleg V. Gerasimenko^¶, Ole H. Petersen^¶, Jeremy D. Milton, and Jonathan M. Rhodes

From the Departments of  Medicine and ^¶ Physiology and ^§ School of Biological Sciences, University of Liverpool, Liverpool L69 3GA, United Kingdom

The Gal1-3GalNAc (TF antigen)-binding lectin (ABL) from the common edible mushroom (Agaricus bisporus) has a potent anti-proliferative effect without any apparent cytotoxicity. This unusual combination of properties prompted investigation of its mechanism of action. In contrast to soluble lectin, agarose-immobilized, and hence noninternalizable ABL had no effect on proliferation of HT29 colon cancer cells. Electron microscopy of HT29 cells incubated with fluorescein- and gold-conjugated ABL showed internalization of the lectin into endocytotic vesicles and multivesicular bodies. Confocal microscopy showed perinuclear accumulation of fluorescein isothiocyanate-conjugated lectin, which also inhibits HT29 cell proliferation, raising the possibility that the lectin might interfere with nuclear pore function. Transport of heat shock protein 70 into the nucleus in response to heat shock was blocked by preincubation of HT29 cells for 6 h with 40 µg/ml ABL. In digitonin-permeabilized cells, nuclear uptake of bovine albumin conjugated to a nuclear localization sequence (NLS)-containing peptide was also inhibited by a 15-min preincubation with 40-100 µg/ml ABL. In contrast, serum-stimulated nuclear translocation of mitogen-activated protein kinase, which is NLS-independent, was not affected by pretreatment of cells with the lectin. These results suggest that the anti-proliferative effect of ABL is likely to be a consequence of the lectin trafficking to the nuclear periphery, where it blocks NLS-dependent protein uptake into the nucleus.

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