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Science 7 July 2000:
Vol. 289. no. 5476, pp. 113 - 116
DOI: 10.1126/science.289.5476.113
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Reports

Cooperative Regulation of Cell Polarity and Growth by Drosophila Tumor Suppressors

David Bilder, 1* Min Li, 2 Norbert Perrimon 12

Loss of cell polarity and tissue architecture are characteristics of malignant cancers derived from epithelial tissues. We provide evidence from Drosophila that a group of membrane-associated proteins act in concert to regulate both epithelial structure and cell proliferation. Scribble (Scrib) is a cell junction-localized protein required for polarization of embryonic and, as demonstrated here, imaginal disc and follicular epithelia. We show that the tumor suppressors lethal giant larvae (lgl) and discs-large (dlg) have identical effects on all three epithelia, and that scrib also acts as a tumor suppressor. Scrib and Dlg colocalize and overlap with Lgl in epithelia; activity of all three genes is required for cortical localization of Lgl and junctional localization of Scrib and Dlg. scrib, dlg, and lgl show strong genetic interactions. Our data indicate that the three tumor suppressors act together in a common pathway to regulate cell polarity and growth control.

1 Department of Genetics and
2 Howard Hughes Medical Institute, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA.
*   To whom correspondence should be addressed. E-mail: bilder{at}rascal.med.harvard.edu

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The Erbin PDZ Domain Binds with High Affinity and Specificity to the Carboxyl Termini of delta -Catenin and ARVCF.
R. P. Laura, A. S. Witt, H. A. Held, R. Gerstner, K. Deshayes, M. F. T. Koehler, K. S. Kosik, S. S. Sidhu, and L. A. Lasky (2002)
J. Biol. Chem. 277, 12906-12914
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The Maguk protein, Pals1, functions as an adapter, linking mammalian homologues of Crumbs and Discs Lost.
M. H. Roh, O. Makarova, C.-J. Liu, Shin, S. Lee, S. Laurinec, M. Goyal, R. Wiggins, and B. Margolis (2002)
J. Cell Biol. 157, 161-172
   Abstract »    Full Text »    PDF »
Assembly of C. elegans apical junctions involves positioning and compaction by LET-413 and protein aggregation by the MAGUK protein DLG-1.
L. McMahon, R. Legouis, J.-L. Vonesch, and M. Labouesse (2002)
J. Cell Sci. 114, 2265-2277
   Abstract »    Full Text »    PDF »
Densin-180 Interacts with delta -Catenin/Neural Plakophilin-related Armadillo Repeat Protein at Synapses.
I. Izawa, M. Nishizawa, K. Ohtakara, and M. Inagaki (2002)
J. Biol. Chem. 277, 5345-5350
   Abstract »    Full Text »    PDF »
Mutational analysis of the discs large tumour suppressor identifies domains responsible for human papillomavirus type 18 E6-mediated degradation.
D. Gardiol, S. Galizzi, and L. Banks (2002)
J. Gen. Virol. 83, 283-289
   Abstract »    Full Text »    PDF »


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