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Article: Deleted in liver cancer (DLC) 2 encodes a RhoGAP protein with growth suppressor function and is underexpressed in hepatocellular carcinoma

TitleDeleted in liver cancer (DLC) 2 encodes a RhoGAP protein with growth suppressor function and is underexpressed in hepatocellular carcinoma
Authors
Issue Date2003
PublisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/
Citation
Journal Of Biological Chemistry, 2003, v. 278 n. 12, p. 10824-10830 How to Cite?
AbstractHepatocellular 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 in liver cancer 2) at 13q12.3 encoding a novel Rho family GTPase-activating protein (GAP). DLC2 mRNA 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 8p22p21.3 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.
Persistent Identifierhttp://hdl.handle.net/10722/68015
ISSN
2015 Impact Factor: 4.258
2015 SCImago Journal Rankings: 3.151
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorChing, YPen_HK
dc.contributor.authorWong, CMen_HK
dc.contributor.authorChan, SFen_HK
dc.contributor.authorLeung, THYen_HK
dc.contributor.authorNg, DCHen_HK
dc.contributor.authorJin, DYen_HK
dc.contributor.authorNg, IOLen_HK
dc.date.accessioned2010-09-06T06:00:31Z-
dc.date.available2010-09-06T06:00:31Z-
dc.date.issued2003en_HK
dc.identifier.citationJournal Of Biological Chemistry, 2003, v. 278 n. 12, p. 10824-10830en_HK
dc.identifier.issn0021-9258en_HK
dc.identifier.urihttp://hdl.handle.net/10722/68015-
dc.description.abstractHepatocellular 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 in liver cancer 2) at 13q12.3 encoding a novel Rho family GTPase-activating protein (GAP). DLC2 mRNA 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 8p22p21.3 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.en_HK
dc.languageengen_HK
dc.publisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/en_HK
dc.relation.ispartofJournal of Biological Chemistryen_HK
dc.rightsJournal of Biological Chemistry. Copyright © American Society for Biochemistry and Molecular Biology, Inc.en_HK
dc.subject.mesh3T3 Cellsen_HK
dc.subject.meshAdulten_HK
dc.subject.meshAgeden_HK
dc.subject.meshAmino Acid Sequenceen_HK
dc.subject.meshAnimalsen_HK
dc.subject.meshCarcinoma, Hepatocellular - geneticsen_HK
dc.subject.meshCell Transformation, Neoplasticen_HK
dc.subject.meshChromosomes, Human, Pair 13en_HK
dc.subject.meshFemaleen_HK
dc.subject.meshGTPase-Activating Proteins - chemistry - genetics - physiologyen_HK
dc.subject.meshGenes, Tumor Suppressoren_HK
dc.subject.meshHumansen_HK
dc.subject.meshLiver Neoplasms - geneticsen_HK
dc.subject.meshLoss of Heterozygosityen_HK
dc.subject.meshMaleen_HK
dc.subject.meshMiceen_HK
dc.subject.meshMiddle Ageden_HK
dc.subject.meshMolecular Sequence Dataen_HK
dc.subject.meshTumor Suppressor Proteins - genetics - physiologyen_HK
dc.titleDeleted in liver cancer (DLC) 2 encodes a RhoGAP protein with growth suppressor function and is underexpressed in hepatocellular carcinomaen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0021-9258&volume=278&issue=12&spage=10824&epage=10830&date=2003&atitle=Deleted+in+liver+cancer+(DLC)+2+encodes+a+RhoGAP+protein+with+growth+suppressor+function+and+is+underexpressed+in+hepatocellular+carcinomaen_HK
dc.identifier.emailChing, YP:ypching@hku.hken_HK
dc.identifier.emailWong, CM:jackwong@pathology.hku.hken_HK
dc.identifier.emailJin, DY:dyjin@hkucc.hku.hken_HK
dc.identifier.emailNg, IOL:iolng@hkucc.hku.hken_HK
dc.identifier.authorityChing, YP=rp00469en_HK
dc.identifier.authorityWong, CM=rp00231en_HK
dc.identifier.authorityJin, DY=rp00452en_HK
dc.identifier.authorityNg, IOL=rp00335en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1074/jbc.M208310200en_HK
dc.identifier.pmid12531887en_HK
dc.identifier.scopuseid_2-s2.0-0037855764en_HK
dc.identifier.hkuros76743en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0037855764&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume278en_HK
dc.identifier.issue12en_HK
dc.identifier.spage10824en_HK
dc.identifier.epage10830en_HK
dc.identifier.isiWOS:000181777500108-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridChing, YP=7005431277en_HK
dc.identifier.scopusauthoridWong, CM=16314668400en_HK
dc.identifier.scopusauthoridChan, SF=7404255795en_HK
dc.identifier.scopusauthoridLeung, THY=7202110922en_HK
dc.identifier.scopusauthoridNg, DCH=36981535100en_HK
dc.identifier.scopusauthoridJin, DY=7201973614en_HK
dc.identifier.scopusauthoridNg, IOL=7102753722en_HK

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