File Download
  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Akt blocks the tumor suppressor activity of LKB1 by promoting phosphorylation-dependent nuclear retention through 14-3-3 proteins

TitleAkt blocks the tumor suppressor activity of LKB1 by promoting phosphorylation-dependent nuclear retention through 14-3-3 proteins
Authors
KeywordsProtein 14-3-3
Protein kinase B
Animal experiment
Breast cancer
Breast carcinogenesis
Issue Date2012
PublisherE-Century Publishing Corporation. The Journal's web site is located at http://www.ajtr.org
Citation
American Journal of Translational Research, 2012, v. 4 n. 2, p. 175-186 How to Cite?
AbstractThe survival kinase Akt and the tumor suppressor LKB1 elicit opposite effects on cell proliferation and tumorigenesis. The present study demonstrates that Akt acts as an upstream kinase of LKB1 to promote the phosphorylation at Ser334 and facilitate its binding to 14-3-3 proteins, resulting in a decreased interaction with STE20-related adaptor protein alpha (STRADalpha) and an enhanced nuclear accumulation of LKB1. The S334A mutant of LKB1 exhibits impaired binding with 14-3-3 proteins and is localized predominantly in the cytoplasm, whereas the phosphorylation-mimic mutant, S334D, is sequestrated in the nuclei and unable to elicit the tumor suppressor function. On the other hand, S334A exerts more potent activity than wild type LKB1 in inhibiting the breast cancer cell proliferation and tumor growth in mice. These findings suggest that Akt blocks the anti-growth signal of LKB1 by triggering a phosphorylation-dependent nuclear sequestration of LKB1 through 14-3-3 proteins.
Persistent Identifierhttp://hdl.handle.net/10722/163480
ISSN
2015 Impact Factor: 3.146
2015 SCImago Journal Rankings: 1.442
PubMed Central ID
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorLiu, Len_HK
dc.contributor.authorSiu, FMen_HK
dc.contributor.authorChe, CMen_HK
dc.contributor.authorXu, Aen_HK
dc.contributor.authorWang, Yen_HK
dc.date.accessioned2012-09-05T05:31:50Z-
dc.date.available2012-09-05T05:31:50Z-
dc.date.issued2012en_HK
dc.identifier.citationAmerican Journal of Translational Research, 2012, v. 4 n. 2, p. 175-186en_HK
dc.identifier.issn1943-8141en_HK
dc.identifier.urihttp://hdl.handle.net/10722/163480-
dc.description.abstractThe survival kinase Akt and the tumor suppressor LKB1 elicit opposite effects on cell proliferation and tumorigenesis. The present study demonstrates that Akt acts as an upstream kinase of LKB1 to promote the phosphorylation at Ser334 and facilitate its binding to 14-3-3 proteins, resulting in a decreased interaction with STE20-related adaptor protein alpha (STRADalpha) and an enhanced nuclear accumulation of LKB1. The S334A mutant of LKB1 exhibits impaired binding with 14-3-3 proteins and is localized predominantly in the cytoplasm, whereas the phosphorylation-mimic mutant, S334D, is sequestrated in the nuclei and unable to elicit the tumor suppressor function. On the other hand, S334A exerts more potent activity than wild type LKB1 in inhibiting the breast cancer cell proliferation and tumor growth in mice. These findings suggest that Akt blocks the anti-growth signal of LKB1 by triggering a phosphorylation-dependent nuclear sequestration of LKB1 through 14-3-3 proteins.en_HK
dc.languageengen_US
dc.publisherE-Century Publishing Corporation. The Journal's web site is located at http://www.ajtr.orgen_HK
dc.relation.ispartofAmerican Journal of Translational Researchen_HK
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subjectProtein 14-3-3en_HK
dc.subjectProtein kinase Ben_HK
dc.subjectAnimal experimenten_HK
dc.subjectBreast canceren_HK
dc.subjectBreast carcinogenesisen_HK
dc.titleAkt blocks the tumor suppressor activity of LKB1 by promoting phosphorylation-dependent nuclear retention through 14-3-3 proteinsen_HK
dc.typeArticleen_HK
dc.identifier.emailSiu, FM: fmsiu@hku.hken_HK
dc.identifier.emailChe, CM: cmche@hku.hken_HK
dc.identifier.emailXu, A: amxu@hku.hk-
dc.identifier.emailWang, Y: yuwanghk@hku.hk-
dc.identifier.authoritySiu, FM=rp00776en_HK
dc.identifier.authorityChe, CM=rp00670en_HK
dc.description.naturepublished_or_final_versionen_US
dc.identifier.pmid22611470-
dc.identifier.pmcidPMC3353533-
dc.identifier.scopuseid_2-s2.0-84860178975en_HK
dc.identifier.hkuros204848-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-84860178975&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume4en_HK
dc.identifier.issue2en_HK
dc.identifier.spage175en_HK
dc.identifier.epage186en_HK
dc.identifier.isiWOS:000318278200004-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridWang, Y=34973733700en_HK
dc.identifier.scopusauthoridXu, A=7202655409en_HK
dc.identifier.scopusauthoridChe, CM=55195481700en_HK
dc.identifier.scopusauthoridSiu, FM=55195027400en_HK
dc.identifier.scopusauthoridLiu, L=21737444900en_HK

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats