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PMID:16951145

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Citation

Yam, JW, Ko, FC, Chan, CY, Jin, DY and Ng, IO (2006) Interaction of deleted in liver cancer 1 with tensin2 in caveolae and implications in tumor suppression. Cancer Res. 66:8367-72

Abstract

Deleted in liver cancer 1 (DLC1) is a recently identified tumor suppressor gene frequently underexpressed in hepatocellular carcinoma (HCC). DLC1 encodes a Rho GTPase-activating protein domain that exhibits growth-suppressive activity in HCC cell lines. Our recent finding has revealed that inhibition of Rho-mediated actin stress fiber formation by DLC1 is associated with its growth inhibitory activity. In the present study, we identified tensin2 as the novel binding partner of DLC1. Tensin2 belongs to a new family of focal adhesion proteins that play key roles in cytoskeleton organization and signal transduction. Dysregulation of tensin proteins has previously been implicated in human cancers. Tensin2 is highly expressed in human liver. Introduction of tensin2 into HCC cell lines with low expression of tensin2 caused significant growth inhibition and induction of apoptosis. Tensin2 directly interacted with DLC1 in vitro and in vivo. Both proteins localized to punctate structures in the cytoplasm. Sequence analysis of DLC1 and tensin2 identified caveolin-1 binding motif in both proteins. In vivo immunoprecipitation study confirmed that both proteins indeed interacted with endogenous caveolin-1, which is the major structural component of caveolae. Our findings presented here suggest a new model for the action of DLC1 in hepatocytes, whereby DLC1-tensin2 complex interacts with Rho GTPases in caveolae to effect cytoskeletal reorganization.

Links

PubMed Online version:10.1158/0008-5472.CAN-05-2850

Keywords

Binding Sites; Carcinoma, Hepatocellular/genetics; Carcinoma, Hepatocellular/metabolism; Caveolae/pathology; Caveolae/physiology; Cell Line; Cell Line, Tumor; Colony-Forming Units Assay; GTPase-Activating Proteins/metabolism; Gene Expression Regulation, Neoplastic; Genes, Reporter; Glutathione Transferase/metabolism; Humans; Kidney; Liver/physiology; Liver Neoplasms/genetics; Liver Neoplasms/metabolism; Microfilament Proteins/genetics; Microfilament Proteins/metabolism; Mutagenesis, Site-Directed; Phosphoric Monoester Hydrolases/genetics; Phosphoric Monoester Hydrolases/metabolism; Transfection; Tumor Suppressor Proteins/genetics; Tumor Suppressor Proteins/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:CAV1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q63HR2

F

Seeded From UniProt

complete

HUMAN:CAV1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q96QB1

F

Seeded From UniProt

complete

HUMAN:TNS2

located_in

GO:0005925: focal adhesion

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:TNS2

involved_in

GO:0008285: negative regulation of cell population proliferation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:TNS2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q03135

F

Seeded From UniProt

complete

HUMAN:RHG07

located_in

GO:0005925: focal adhesion

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:RHG07

located_in

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:RHG07

located_in

GO:0005901: caveola

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:RHG07

involved_in

GO:0035024: negative regulation of Rho protein signal transduction

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:RHG07

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q63HR2

F

Seeded From UniProt

complete

HUMAN:RHG07

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q03135

F

Seeded From UniProt

complete


See also

References

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