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PMID: 12202036 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

salvador Promotes both cell cycle exit and apoptosis in Drosophila and is mutated in human cancer cell lines.

Cell ·Vol. 110 ·No. 4 ·2002-08-23 ·Pages 467-78

Tapon N, Harvey KF, Bell DW, Wahrer DC, Schiripo TA, Haber D, Hariharan IK

Abstract

The number of cells in an organism is determined by regulating both cell proliferation and cell death. Relatively few mechanisms have been identified that can modulate both of these processes. In a screen for Drosophila mutations that result in tissue overgrowth, we identified salvador (sav), a gene that promotes both cell cycle exit and cell death. Elevated Cyclin E and DIAP1 levels are found in mutant cells, resulting in delayed cell cycle exit and impaired apoptosis. Salvador contains two WW domains and binds to the Warts (or LATS) protein kinase. The human ortholog of salvador (hWW45) is mutated in three cancer cell lines. Thus, salvador restricts cell numbers in vivo by functioning as a dual regulator of cell proliferation and apoptosis.

MeSH Terms

Amino Acid Sequence Animals Apoptosis/genetics Base Sequence/genetics Cell Cycle Proteins/genetics,isolation & purification Cell Division/genetics Cell Transformation, Neoplastic/genetics Drosophila Proteins/genetics,isolation & purification Eukaryotic Cells/metabolism,pathology Eye/embryology,metabolism,ultrastructure Eye Abnormalities/genetics,metabolism,pathology Female Gene Expression Regulation, Developmental/genetics Gene Expression Regulation, Neoplastic/genetics Genes, cdc/physiology Genetic Testing Humans Male Molecular Sequence Data Mutation/genetics Neoplasms/genetics,metabolism,pathology Phenotype Photoreceptor Cells, Invertebrate/abnormalities,metabolism,pathology Protein Kinases Protein Serine-Threonine Kinases/genetics,metabolism Protein Structure, Tertiary/genetics Proteins/genetics,metabolism Tumor Cells, Cultured

Chemicals

Cell Cycle Proteins Drosophila Proteins Proteins SAV1 protein, human sav protein, Drosophila Protein Kinases LATS1 protein, human wts protein, Drosophila Protein Serine-Threonine Kinases

Authors & Affiliations

7 authors, click to expand affiliations / ORCID

Tapon Nicolas

Massachusetts General Hospital Cancer Center, Building 149, 13th Street, Charlestown 02129, USA.

Harvey Kieran F

Bell Daphne W

Wahrer Doke C R

Schiripo Taryn A

Haber Daniel A

Hariharan Iswar K

Article Info

Journal

Cell

Abbr.

Cell

ISSN

0092-8674

DOI

10.1016/s0092-8674(02)00824-3

Published

2002-08-23

Pages

467-78

Language

English

Region

United States

NLM ID

0413066

Subset

Grants

NCI NIH HHS · CA87691 · United States

NEI NIH HHS · EY11632 · United States

NIGMS NIH HHS · GM61672 · United States

Corrections

CommentIn

PMID: 12202030

External Links

PubMed source DOI: 10.1016/s0092-8674(02)00824-3 View journal details

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salvador Promotes both cell cycle exit and apoptosis in Drosophila and is mutated in human cancer cell lines.

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