DOCK4, a GTPase activator, is disrupted during tumorigenesis

Yajnik, V., Paulding, C., Sordella, R., McClatchey, A. I., Saito, M., Wahrer, D. C., Reynolds, P., Bell, D. W., Lake, R., van den Heuvel, S., Settleman, J., Haber, D. A. (March 2003) DOCK4, a GTPase activator, is disrupted during tumorigenesis. Cell, 112 (5). pp. 673-84. ISSN 0092-8674 (Print)

Abstract

We used representational difference analysis to identify homozygous genomic deletions selected during tumor progression in the mouse NF2 and TP53 tumor model. We describe a deletion targeting DOCK4, a member of the CDM gene family encoding regulators of small GTPases. DOCK4 specifically activates Rap GTPase, enhancing the formation of adherens junctions. DOCK4 mutations are present in a subset of human cancer cell lines; a recurrent missense mutant identified in human prostate and ovarian cancers encodes a protein that is defective in Rap1 activation. The engulfment defect of C. elegans mutants lacking the CDM gene ced-5 is rescued by wild-type DOCK4, but not by the mutant allele. Expression of wild-type, but not mutant, DOCK4 in mouse osteosarcoma cells with a deletion of the endogenous gene suppresses growth in soft agar and tumor invasion in vivo. DOCK4 therefore encodes a CDM family member that regulates intercellular junctions and is disrupted during tumorigenesis.

Item Type:	Paper
Uncontrolled Keywords:	Animals Bone Neoplasms genetics metabolism Caenorhabditis elegans Cell Transformation Neoplastic genetics metabolism Eukaryotic Cells metabolism GTPase-Activating Proteins genetics isolation & purification Gene Deletion Gene Expression Regulation Neoplastic genetics physiology Gene Silencing physiology Genes Regulator genetics Homozygote Humans Mice Mice Mutant Strains Molecular Sequence Data Mutation genetics Osteosarcoma genetics metabolism Sequence Homology Amino Acid Sequence Homology Nucleic Acid Tumor Cells Cultured enzymology rap GTP-Binding Proteins/genetics metabolism
Subjects:	diseases & disorders > cancer bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > GTPase bioinformatics > genomics and proteomics > genetics & nucleic acid processing bioinformatics > genomics and proteomics bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene expression bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene regulation bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene regulation bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function organism description > animal > mammal > rodent > mouse
CSHL Authors:	Sordella, Raffaella
Communities:	CSHL labs > Sordella lab
Depositing User:	CSHL Librarian
Date:	7 March 2003
Date Deposited:	09 May 2012 18:02
Last Modified:	13 Mar 2013 16:18
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/26246

Actions (login required)

Administrator's edit/view item