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Article: Deleted in liver cancer 1 (DLC1) utilizes a novel binding site for tensin2 PTB domain interaction and is required for tumor-suppressive function

TitleDeleted in liver cancer 1 (DLC1) utilizes a novel binding site for tensin2 PTB domain interaction and is required for tumor-suppressive function
Authors
Issue Date2009
PublisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action
Citation
PLoS One, 2009, v. 4 n. 5, p. e5572c How to Cite?
AbstractBackground: Deleted in liver cancer 1 (DLC1) is a Rho GTPase-activating protein (RhoGAP) frequently deleted and underexpressed in hepatocellular carcinoma (HCC) as well as in other cancers. Recent independent studies have shown interaction of DLC1 with members of the tensin focal adhesion protein family in a Src Homology 2 (SH2) domain-dependent mechanism. DLC1 and tensins interact and co-localize to punctate structures at focal adhesions. However, the mechanisms underlying the interaction between DLC1 and various tensins remain controversial. Methodology/Principal Findings: We used a co-immunoprecipitation assay to identify a previously undocumented binding site at 375-385 of DLC1 that predominantly interacted with the phosphotyrosine binding (PTB) domain of tensin2. DLC1-tensin2 interaction is completely abolished in a DLC1 mutant lacking this novel PTB binding site (DLC1ΔPTB). However, as demonstrated by immunofluorescence and co-immunoprecipitation, neither the focal adhesion localization nor the interaction with tensin1 and C-terminal tensin-like (cten) were affected. Interestingly, the functional significance of this novel site was exhibited by the partial reduction of the RhoGAP activity, which, in turn, attenuated the growth-suppressive activity of DLC1 upon its removal from DLC1. Conclusions/Significance: This study has provided new evidence that DLC1 also interacts with tensin2 in a PTB domain-dependent manner. In addition to properly localizing focal adhesions and preserving RhoGAP activity, DLC1 interaction with tensin2 through this novel focal adhesion binding site contributes to the growth-suppressive activity of DLC1. © 2009 Chan et al.
Persistent Identifierhttp://hdl.handle.net/10722/60567
ISSN
2015 Impact Factor: 3.057
2015 SCImago Journal Rankings: 1.395
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorChan, LKen_HK
dc.contributor.authorKo, FCFen_HK
dc.contributor.authorNg, IOLen_HK
dc.contributor.authorYam, JWPen_HK
dc.date.accessioned2010-05-31T04:13:49Z-
dc.date.available2010-05-31T04:13:49Z-
dc.date.issued2009en_HK
dc.identifier.citationPLoS One, 2009, v. 4 n. 5, p. e5572cen_HK
dc.identifier.issn1932-6203en_HK
dc.identifier.urihttp://hdl.handle.net/10722/60567-
dc.description.abstractBackground: Deleted in liver cancer 1 (DLC1) is a Rho GTPase-activating protein (RhoGAP) frequently deleted and underexpressed in hepatocellular carcinoma (HCC) as well as in other cancers. Recent independent studies have shown interaction of DLC1 with members of the tensin focal adhesion protein family in a Src Homology 2 (SH2) domain-dependent mechanism. DLC1 and tensins interact and co-localize to punctate structures at focal adhesions. However, the mechanisms underlying the interaction between DLC1 and various tensins remain controversial. Methodology/Principal Findings: We used a co-immunoprecipitation assay to identify a previously undocumented binding site at 375-385 of DLC1 that predominantly interacted with the phosphotyrosine binding (PTB) domain of tensin2. DLC1-tensin2 interaction is completely abolished in a DLC1 mutant lacking this novel PTB binding site (DLC1ΔPTB). However, as demonstrated by immunofluorescence and co-immunoprecipitation, neither the focal adhesion localization nor the interaction with tensin1 and C-terminal tensin-like (cten) were affected. Interestingly, the functional significance of this novel site was exhibited by the partial reduction of the RhoGAP activity, which, in turn, attenuated the growth-suppressive activity of DLC1 upon its removal from DLC1. Conclusions/Significance: This study has provided new evidence that DLC1 also interacts with tensin2 in a PTB domain-dependent manner. In addition to properly localizing focal adhesions and preserving RhoGAP activity, DLC1 interaction with tensin2 through this novel focal adhesion binding site contributes to the growth-suppressive activity of DLC1. © 2009 Chan et al.en_HK
dc.languageengen_HK
dc.publisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.actionen_HK
dc.relation.ispartofPLoS ONEen_HK
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.titleDeleted in liver cancer 1 (DLC1) utilizes a novel binding site for tensin2 PTB domain interaction and is required for tumor-suppressive functionen_HK
dc.typeArticleen_HK
dc.identifier.emailNg, IOL:iolng@hkucc.hku.hken_HK
dc.identifier.emailYam, JWP:judyyam@pathology.hku.hken_HK
dc.identifier.authorityNg, IOL=rp00335en_HK
dc.identifier.authorityYam, JWP=rp00468en_HK
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1371/journal.pone.0005572en_HK
dc.identifier.scopuseid_2-s2.0-65949099133en_HK
dc.identifier.hkuros156764en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-65949099133&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume4en_HK
dc.identifier.issue5en_HK
dc.identifier.spagee5572cen_HK
dc.identifier.epagee5572cen_HK
dc.identifier.isiWOS:000266107400015-
dc.publisher.placeUnited Statesen_HK

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