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Conference Paper: C20, a novel binding partner of DLC1 identified by yeast-2-hybrid screening

TitleC20, a novel binding partner of DLC1 identified by yeast-2-hybrid screening
Authors
Issue Date2006
PublisherAmerican Association for Cancer Research
Citation
The 97th AACR Annual Meeting, Washington, D.C., 1-5 April 2006. In Cancer Research, 2006, v. 66 n. 8S, p. 966 Abstract no. 4105 How to Cite?
AbstractHepatocellular carcinoma (HCC) is the fifth most common malignancies worldwide. Although the risk factors are known, the molecular and cellular mechanism of hepatocarcinogenesis is still unclear. Deleted in Liver Cancer 1(DLC1) is a recently identified tumor suppressor gene and the DLC1 gene encodes a RhoGAP protein, switching the active GTP bound form of small monomeric G-protein, Rho, into the inactive GDP bound form. We have previously shown that it is frequently underexpressed in HCC. We have also characterized DLC1 to be a growth suppressor in HCC cell lines and documented its in vitro RhoGAP activity. Our recent findings have also revealed that inhibition of Rho-mediated actin stress fiber formation by DLC1 is associated with its growth suppressive effect. Although DLC1 has multiple domains, the potential molecular targets and binding partners remain unclear. With the employment of yeast-2-hybrid system to screen against the human liver cDNA library, we have identified a yeast clone, namely clone 20 (C20), as a novel binding partner of DLC1. C20 contains a partial, unknown protein encoding DNA sequence of approximately 600 base pairs corresponding to human chromosome 19p13.3. C20 has a high sequence homology to the mouse Gtrgeo22 gene, which encodes a novel transmembrane protein containing dileucine and tyrosine-based motifs. Previous report has pointed out that mutation of Gtrgeo22can cause multiple defects in mice including male sterility. C20 is expressed in human liver and the transcripts are detectable by RT-PCR in all 10 HCC cell lines we have screened. The minimal interacting domain of DLC1 with C20 protein was mapped to the residues 293-647 of DLC1 in SFY526 yeast cells. Our results showed that DLC1 specifically interacted with C20, which is therefore a novel binding partner of DLC1. Further studies will derive new insight into the biological functions of DLC1. (This study was funded in part by the Michael Kadoorie Cancer Genetic Research Program of the Kadoorie Charitable Foundation)
Persistent Identifierhttp://hdl.handle.net/10722/104797
ISSN
2015 Impact Factor: 8.556
2015 SCImago Journal Rankings: 5.372

 

DC FieldValueLanguage
dc.contributor.authorChan, LKen_HK
dc.contributor.authorYam, JWPen_HK
dc.contributor.authorNg, IOLen_HK
dc.date.accessioned2010-09-25T22:07:44Z-
dc.date.available2010-09-25T22:07:44Z-
dc.date.issued2006en_HK
dc.identifier.citationThe 97th AACR Annual Meeting, Washington, D.C., 1-5 April 2006. In Cancer Research, 2006, v. 66 n. 8S, p. 966 Abstract no. 4105-
dc.identifier.issn0008-5472-
dc.identifier.urihttp://hdl.handle.net/10722/104797-
dc.description.abstractHepatocellular carcinoma (HCC) is the fifth most common malignancies worldwide. Although the risk factors are known, the molecular and cellular mechanism of hepatocarcinogenesis is still unclear. Deleted in Liver Cancer 1(DLC1) is a recently identified tumor suppressor gene and the DLC1 gene encodes a RhoGAP protein, switching the active GTP bound form of small monomeric G-protein, Rho, into the inactive GDP bound form. We have previously shown that it is frequently underexpressed in HCC. We have also characterized DLC1 to be a growth suppressor in HCC cell lines and documented its in vitro RhoGAP activity. Our recent findings have also revealed that inhibition of Rho-mediated actin stress fiber formation by DLC1 is associated with its growth suppressive effect. Although DLC1 has multiple domains, the potential molecular targets and binding partners remain unclear. With the employment of yeast-2-hybrid system to screen against the human liver cDNA library, we have identified a yeast clone, namely clone 20 (C20), as a novel binding partner of DLC1. C20 contains a partial, unknown protein encoding DNA sequence of approximately 600 base pairs corresponding to human chromosome 19p13.3. C20 has a high sequence homology to the mouse Gtrgeo22 gene, which encodes a novel transmembrane protein containing dileucine and tyrosine-based motifs. Previous report has pointed out that mutation of Gtrgeo22can cause multiple defects in mice including male sterility. C20 is expressed in human liver and the transcripts are detectable by RT-PCR in all 10 HCC cell lines we have screened. The minimal interacting domain of DLC1 with C20 protein was mapped to the residues 293-647 of DLC1 in SFY526 yeast cells. Our results showed that DLC1 specifically interacted with C20, which is therefore a novel binding partner of DLC1. Further studies will derive new insight into the biological functions of DLC1. (This study was funded in part by the Michael Kadoorie Cancer Genetic Research Program of the Kadoorie Charitable Foundation)-
dc.languageengen_HK
dc.publisherAmerican Association for Cancer Research-
dc.relation.ispartofCancer Researchen_HK
dc.titleC20, a novel binding partner of DLC1 identified by yeast-2-hybrid screeningen_HK
dc.typeConference_Paperen_HK
dc.identifier.emailChan, LK: lokongchan@gmail.comen_HK
dc.identifier.emailYam, JWP: judyyam@pathology.hku.hken_HK
dc.identifier.emailNg, IOL: iolng@hkucc.hku.hken_HK
dc.identifier.authorityYam, JWP=rp00468en_HK
dc.identifier.authorityNg, IOL=rp00335en_HK
dc.identifier.hkuros120070en_HK

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