hScrib is a functional homologue of the Drosophila tumour suppressor Scribble.
Scribble (scrib), discs large (dlg) and lethal giant larvae (lgl) encode proteins that regulate cell polarity and have been identified as neoplastic tumour suppressor genes in Drosophila melanogaster. Here, we have used the Drosophila model system to provide the first functional evidence that human Scribble (hScrib) can act as a tumour suppressor. We show that hScrib protein displays highly polarized localization in mammalian epithelial cells and colocalizes with mammalian Dlg, similar to D. melanogaster Scribble (DmScrib) distribution in Drosophila epithelium. Furthermore, hScrib can rescue the polarity and tumorous overgrowth defects of scrib mutant Drosophila. hScrib therefore can act as an effective tumour suppressor in vivo, regulating both apical-basal polarity and cellular proliferation in a manner similar to that of DmScrib in Drosophila. These data demonstrate that hScrib is a functional homologue of DmScrib and therefore predict an important role for hScrib in the suppression of mammalian tumorigenesis.
Dow
Lukas E
LE
Cell Cycle and Cancer Genetics Laboratory, Peter MacCallum Cancer Centre, St Andrew's Place, East Melbourne, Victoria 3002, Australia.
Brumby
Anthony M
AM
Muratore
Rosa
R
Coombe
Michelle L
ML
Sedelies
Karin A
KA
Trapani
Joseph A
JA
Russell
Sarah M
SM
Richardson
Helena E
HE
Humbert
Patrick O
PO
D000483:Alleles; D000818:Animals; D029721:Drosophila Proteins / Q000235:genetics*; D004331:Drosophila melanogaster; D005260:Female; D016147:Genes, Tumor Suppressor; D005838:Genotype; D049452:Green Fluorescent Proteins; D006579:Heterozygote; D006801:Humans; D008164:Luminescent Proteins / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008856:Microscopy, Fluorescence; D008957:Models, Genetic; D009154:Mutation; D010641:Phenotype; D025521:Tumor Suppressor Proteins
D029721:Drosophila Proteins; D008164:Luminescent Proteins; D008565:Membrane Proteins; C480591:SCRIB protein, human; C404683:Scrib protein, Drosophila; D025521:Tumor Suppressor Proteins; D049452:Green Fluorescent Proteins