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Deleted in Liver Cancer (DLC) 2 Encodes a RhoGAP Protein with Growth Suppressor Function and Is Underexpressed in Hepatocellular Carcinoma
- Source :
- Journal of Biological Chemistry. 278:10824-10830
- Publication Year :
- 2003
- Publisher :
- Elsevier BV, 2003.
-
Abstract
- Hepatocellular carcinoma (HCC) is a major malignancy in many parts of the world, especially in Asia and Africa. Loss of heterozygosity (LOH) on the long arm of chromosome 13 has been reported in HCC. In search of tumor suppressor genes in this region, here we have identified DLC2 (for deleted inliver cancer 2) at 13q12.3 encoding a novel Rho family GTPase-activating protein (GAP). DLC2mRNA is ubiquitously expressed in normal tissues but was significantly underexpressed in 18% (8/45) of human HCCs.DLC2 is homologous to DLC1, a previously identified tumor suppressor gene at 8p22-p21.3 frequently deleted in HCC. DLC2 encodes a novel protein with a RhoGAP domain, a SAM (sterile α motif) domain related to p73/p63, and a lipid-binding StAR-related lipid transfer (START) domain. Biochemical analysis indicates that DLC2 protein has GAP activity specific for small GTPases RhoA and Cdc42. Expression of the GAP domain of DLC2 sufficiently inhibits the Rho-mediated formation of actin stress fibers. Introduction of human DLC2 into mouse fibroblasts suppresses Ras signaling and Ras-induced cellular transformation in a GAP-dependent manner. Taken together, our findings suggest a role for DLC2 in growth suppression and hepatocarcinogenesis.
- Subjects :
- Adult
Male
Carcinoma, Hepatocellular
RHOA
Tumor suppressor gene
Molecular Sequence Data
Loss of Heterozygosity
RhoGAP domain
GTPase
CDC42
Biochemistry
law.invention
Loss of heterozygosity
Mice
law
Animals
Humans
Genes, Tumor Suppressor
Amino Acid Sequence
Molecular Biology
Aged
Genetics
Chromosomes, Human, Pair 13
biology
Tumor Suppressor Proteins
GTPase-Activating Proteins
Liver Neoplasms
3T3 Cells
Cell Biology
Middle Aged
Cell Transformation, Neoplastic
Cancer research
biology.protein
Suppressor
Female
DLC1
Subjects
Details
- ISSN :
- 00219258
- Volume :
- 278
- Database :
- OpenAIRE
- Journal :
- Journal of Biological Chemistry
- Accession number :
- edsair.doi.dedup.....0a62ba43ff3ac2c05806c4255da6fdf4