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Article: PKA-induced dimerization of the RhoGAP DLC1 promotes its inhibition of tumorigenesis and metastasis

TitlePKA-induced dimerization of the RhoGAP DLC1 promotes its inhibition of tumorigenesis and metastasis
Authors
Issue Date2013
Citation
Nature Communications, 2013, v. 4, p. 1618 How to Cite?
AbstractDeleted in Liver Cancer 1 (DLC1) is a tumour suppressor that encodes a RhoGTPase-activating protein (RhoGAP) and is frequently inactivated in many human cancers. The RhoGAP activity of DLC1 against Rho signalling is well documented and is strongly associated with the tumour suppressor functions of DLC1. However, the mechanism by which the RhoGAP activity of DLC1 is regulated remains obscure. Here, we report that phosphorylation of DLC1 at Ser549 by cyclic AMP-dependent protein kinase A contributes to enhanced RhoGAP activity and promotes the activation of DLC1, which suppresses hepatoma cell growth, motility and metastasis in both in vitro and in vivo models. Intriguingly, we found that Ser549 phosphorylation induces the dimerization of DLC1 and that inducible dimerization of DLC1 can rescue the tumour suppressive and RhoGAP activities of DLC1 containing a Ser549 deletion. Our study establishes a novel regulatory mechanism for DLC1 RhoGAP activity via dimerization induced by protein kinase A signalling. © 2013 Macmillan Publishers Limited. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/182048
ISSN
2015 Impact Factor: 11.329
2015 SCImago Journal Rankings: 6.539

 

DC FieldValueLanguage
dc.contributor.authorKo, FCFen_US
dc.contributor.authorChan, LKen_US
dc.contributor.authorSze, MFen_US
dc.contributor.authorYeung, YSen_US
dc.contributor.authorTse, EYTen_US
dc.contributor.authorLu, Pen_US
dc.contributor.authorYu, MHen_US
dc.contributor.authorNg, IOLen_US
dc.contributor.authorYam, JWPen_US
dc.date.accessioned2013-04-17T07:20:28Z-
dc.date.available2013-04-17T07:20:28Z-
dc.date.issued2013en_US
dc.identifier.citationNature Communications, 2013, v. 4, p. 1618en_US
dc.identifier.issn2041-1723-
dc.identifier.urihttp://hdl.handle.net/10722/182048-
dc.description.abstractDeleted in Liver Cancer 1 (DLC1) is a tumour suppressor that encodes a RhoGTPase-activating protein (RhoGAP) and is frequently inactivated in many human cancers. The RhoGAP activity of DLC1 against Rho signalling is well documented and is strongly associated with the tumour suppressor functions of DLC1. However, the mechanism by which the RhoGAP activity of DLC1 is regulated remains obscure. Here, we report that phosphorylation of DLC1 at Ser549 by cyclic AMP-dependent protein kinase A contributes to enhanced RhoGAP activity and promotes the activation of DLC1, which suppresses hepatoma cell growth, motility and metastasis in both in vitro and in vivo models. Intriguingly, we found that Ser549 phosphorylation induces the dimerization of DLC1 and that inducible dimerization of DLC1 can rescue the tumour suppressive and RhoGAP activities of DLC1 containing a Ser549 deletion. Our study establishes a novel regulatory mechanism for DLC1 RhoGAP activity via dimerization induced by protein kinase A signalling. © 2013 Macmillan Publishers Limited. All rights reserved.-
dc.languageengen_US
dc.relation.ispartofNature Communicationsen_US
dc.titlePKA-induced dimerization of the RhoGAP DLC1 promotes its inhibition of tumorigenesis and metastasisen_US
dc.typeArticleen_US
dc.identifier.emailKo, FCF: bokcf@hku.hken_US
dc.identifier.emailChan, LK: lkchan1@hku.hken_US
dc.identifier.emailSze, MF: karensze@hkucc.hku.hken_US
dc.identifier.emailYeung, YS: yeungys@hku.hken_US
dc.identifier.emailTse, EYT: edithtse@graduate.hku.hken_US
dc.identifier.emailLu, P: luping@hku.hken_US
dc.identifier.emailNg, IOL: iolng@hku.hken_US
dc.identifier.emailYam, JWP: judyyam@pathology.hku.hken_US
dc.identifier.authorityNg, IOL=rp00335en_US
dc.identifier.authorityYam, JWP=rp00468en_US
dc.identifier.doi10.1038/ncomms2604-
dc.identifier.pmid23511482-
dc.identifier.scopuseid_2-s2.0-84875897562-
dc.identifier.hkuros213877en_US
dc.identifier.volume4en_US
dc.identifier.spage1618en_US
dc.identifier.epage1618en_US

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