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PMID: 10617573 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Drosophila tumor suppressor PTEN controls cell size and number by antagonizing the Chico/PI3-kinase signaling pathway.

Genes & development ·Vol. 13 ·No. 24 ·1999-12-15 ·Pages 3244-58

Goberdhan DC, Paricio N, Goodman EC, Mlodzik M, Wilson C

Abstract

The human tumor suppressor gene PTEN encodes a putative cytoskeleton-associated molecule with both protein phosphatase and phosphatidylinositol 3,4,5-trisphosphate (PIP3) 3-phosphatase activities. In cell culture, the lipid phosphatase activity of this protein is involved in regulating cell proliferation and survival, but the mechanism by which PTEN inhibits tumorigenesis in vivo is not fully established. Here we show that the highly evolutionarily conserved Drosophila PTEN homolog, DPTEN, suppresses hyperplastic growth in flies by reducing cell size and number. We demonstrate that DPTEN modulates tissue mass by acting antagonistically to the Drosophila Class I phosphatidylinositol 3-kinase, Dp110, and its upstream activator Chico, an insulin receptor substrate homolog. Surprisingly, although DPTEN does not generally affect cell fate determination, it does appear to regulate the subcellular organization of the actin cytoskeleton in multiple cell types. From these data, we propose that DPTEN has a complex role in regulating tissue and body size. It acts in opposition to Dp110 to control cell number and growth, while coordinately influencing events at the cell periphery via its effects on the actin cytoskeleton.

MeSH Terms
Amino Acid Sequence Animals Base Sequence Carrier Proteins Cell Division Cell Size Chromosome Mapping Cytoskeleton/physiology Drosophila Proteins Drosophila melanogaster/genetics,growth & development Ethyl Methanesulfonate Eye/cytology,growth & development Genes, Tumor Suppressor Genomic Library Germ-Line Mutation Homozygote Humans Insect Proteins/metabolism Insulin Receptor Substrate Proteins Intracellular Signaling Peptides and Proteins Molecular Sequence Data Mutagenesis PTEN Phosphohydrolase Phosphatidylinositol 3-Kinases/metabolism Phosphoric Monoester Hydrolases/genetics,metabolism Signal Transduction/physiology Transcription, Genetic Tumor Suppressor Proteins Wings, Animal/cytology,growth & development
Chemicals
Carrier Proteins Drosophila Proteins Insect Proteins Insulin Receptor Substrate Proteins Intracellular Signaling Peptides and Proteins Tumor Suppressor Proteins chico protein, Drosophila Ethyl Methanesulfonate Phosphatidylinositol 3-Kinases Phosphoric Monoester Hydrolases PTEN Phosphohydrolase PTEN protein, human
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Goberdhan D C
Research School of Biosciences, Department of Biosciences, University of Kent, Canterbury, Kent CT2 7NJ, United Kingdom.
Paricio N
Goodman E C
Mlodzik M
Wilson C
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.13.24.3244
Published
1999-12-15
Pages
3244-58
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC317204
Subset
IM
Grants
Wellcome Trust · United Kingdom
Databases
GENBANK
AF201904, AF201905, AF201906, AF201907
External Links
PubMed source DOI: 10.1101/gad.13.24.3244 PMC Full Text View journal details
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