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Article: Interleukin-2 induces NF-κB activation through BCL10 and affects its subcellular localization in natural killer lymphoma cells

TitleInterleukin-2 induces NF-κB activation through BCL10 and affects its subcellular localization in natural killer lymphoma cells
Authors
KeywordsB
BCL10
IL2
NF-κ
NK cell lymphoma
Nucleus
Issue Date2010
PublisherJohn Wiley & Sons. The Journal's web site is located at http://www3.interscience.wiley.com/cgi-bin/jhome/1130
Citation
Journal Of Pathology, 2010, v. 221 n. 2, p. 164-174 How to Cite?
AbstractDeregulation of nuclear factor (NF)-κB signalling is common in cancers and is essential for tumourigenesis. Constitutive NF-κB activation in extranodal natural killer (NK)-cell lymphoma, nasal type (ENKL) is known to be associated with aberrant nuclear translocation of BCL10. Here we investigated the mechanisms leading to NF-κB activation and BCL10 nuclear localization in ENKLs. Given that ENKLs are dependent on T-cell-derived interleukin-2 (IL2) for cytotoxicity and proliferation, we investigated whether IL2 modulates NF-κB activation and BCL10 subcellular localization in ENKLs. In the present study, IL2-activated NK lymphoma cells were found to induce NF-κB activation via the PI3K/Akt pathway, leading to an increase in the entry of G 2/M phase and concomitant transcription of NF-κB-responsive genes. We also found that BCL10, a key mediator of NF-κB signalling, participates in the cytokine receptor-induced activation of NF-κB. Knockdown of BCL10 expression resulted in deficient NF-κB signalling, whereas Akt activation was unaffected. Our results suggest that BCL10 plays a role downstream of Akt in the IL2-triggered NF-κB signalling pathway. Moreover, the addition of IL2 to NK cells led to aberrant nuclear translocation of BCL10, which is a pathological feature of ENKLs. We further show that BCL10 can bind to BCL3, a transcriptional co-activator and nuclear protein. Up-regulation of BCL3 expression was observed in response to IL2. Similar to BCL10, the expression and nuclear translocation of BCL3 were induced by IL2 in an Akt-dependent manner. The nuclear translocation of BCL10 was also dependent on BCL3 because silencing BCL3 by RNA interference abrogated this translocation. We identified a critical role for BCL10 in the cytokine receptor-induced NF-κB signalling pathway, which is essential for NK cell activation. We also revealed the underlying mechanism that controls BCL10 nuclear translocation in NK cells. Our findings provide insight into a molecular network within the NF-κB signalling pathway that promotes the pathogenesis of NK cell lymphomas. Copyright © 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Persistent Identifierhttp://hdl.handle.net/10722/148621
ISSN
2014 Impact Factor: 7.429
2014 SCImago Journal Rankings: 3.612
ISI Accession Number ID
Funding AgencyGrant Number
Research Grants Council of Hong Kong, ChinaHKU 7583/54M
Funding Information:

This study was supported by the General Research Fund (GRF) of the Research Grants Council of Hong Kong, China (HKU 7583/54M to GS and RHS).

References

 

DC FieldValueLanguage
dc.contributor.authorChan, KKen_HK
dc.contributor.authorShen, Len_HK
dc.contributor.authorAu, WYen_HK
dc.contributor.authorYuen, HFen_HK
dc.contributor.authorWong, KYen_HK
dc.contributor.authorGuo, Ten_HK
dc.contributor.authorWong, MLYen_HK
dc.contributor.authorShimizu, Nen_HK
dc.contributor.authorTsuchiyama, Jen_HK
dc.contributor.authorKwong, YLen_HK
dc.contributor.authorLiang, RHSen_HK
dc.contributor.authorSrivastava, Gen_HK
dc.date.accessioned2012-05-29T06:14:09Z-
dc.date.available2012-05-29T06:14:09Z-
dc.date.issued2010en_HK
dc.identifier.citationJournal Of Pathology, 2010, v. 221 n. 2, p. 164-174en_HK
dc.identifier.issn0022-3417en_HK
dc.identifier.urihttp://hdl.handle.net/10722/148621-
dc.description.abstractDeregulation of nuclear factor (NF)-κB signalling is common in cancers and is essential for tumourigenesis. Constitutive NF-κB activation in extranodal natural killer (NK)-cell lymphoma, nasal type (ENKL) is known to be associated with aberrant nuclear translocation of BCL10. Here we investigated the mechanisms leading to NF-κB activation and BCL10 nuclear localization in ENKLs. Given that ENKLs are dependent on T-cell-derived interleukin-2 (IL2) for cytotoxicity and proliferation, we investigated whether IL2 modulates NF-κB activation and BCL10 subcellular localization in ENKLs. In the present study, IL2-activated NK lymphoma cells were found to induce NF-κB activation via the PI3K/Akt pathway, leading to an increase in the entry of G 2/M phase and concomitant transcription of NF-κB-responsive genes. We also found that BCL10, a key mediator of NF-κB signalling, participates in the cytokine receptor-induced activation of NF-κB. Knockdown of BCL10 expression resulted in deficient NF-κB signalling, whereas Akt activation was unaffected. Our results suggest that BCL10 plays a role downstream of Akt in the IL2-triggered NF-κB signalling pathway. Moreover, the addition of IL2 to NK cells led to aberrant nuclear translocation of BCL10, which is a pathological feature of ENKLs. We further show that BCL10 can bind to BCL3, a transcriptional co-activator and nuclear protein. Up-regulation of BCL3 expression was observed in response to IL2. Similar to BCL10, the expression and nuclear translocation of BCL3 were induced by IL2 in an Akt-dependent manner. The nuclear translocation of BCL10 was also dependent on BCL3 because silencing BCL3 by RNA interference abrogated this translocation. We identified a critical role for BCL10 in the cytokine receptor-induced NF-κB signalling pathway, which is essential for NK cell activation. We also revealed the underlying mechanism that controls BCL10 nuclear translocation in NK cells. Our findings provide insight into a molecular network within the NF-κB signalling pathway that promotes the pathogenesis of NK cell lymphomas. Copyright © 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.en_HK
dc.languageengen_US
dc.publisherJohn Wiley & Sons. The Journal's web site is located at http://www3.interscience.wiley.com/cgi-bin/jhome/1130en_HK
dc.relation.ispartofJournal of Pathologyen_HK
dc.subjectBen_HK
dc.subjectBCL10en_HK
dc.subjectIL2en_HK
dc.subjectNF-κen_HK
dc.subjectNK cell lymphomaen_HK
dc.subjectNucleusen_HK
dc.subject.meshAdaptor Proteins, Signal Transducing - Genetics - Metabolismen_US
dc.subject.meshCell Lineen_US
dc.subject.meshCell Nucleus - Metabolismen_US
dc.subject.meshGene Expression Regulation - Geneticsen_US
dc.subject.meshHumansen_US
dc.subject.meshInterleukin-2 - Pharmacology - Physiologyen_US
dc.subject.meshLymphoma, Extranodal Nk-T-Cell - Metabolismen_US
dc.subject.meshNf-Kappa B - Genetics - Metabolismen_US
dc.subject.meshProto-Oncogene Proteins - Metabolismen_US
dc.subject.meshProto-Oncogene Proteins C-Akt - Metabolismen_US
dc.subject.meshSignal Transduction - Geneticsen_US
dc.subject.meshTranscription Factors - Metabolismen_US
dc.titleInterleukin-2 induces NF-κB activation through BCL10 and affects its subcellular localization in natural killer lymphoma cellsen_HK
dc.typeArticleen_HK
dc.identifier.emailKwong, YL:ylkwong@hku.hken_HK
dc.identifier.emailLiang, RHS:rliang@hku.hken_HK
dc.identifier.emailSrivastava, G:gopesh@pathology.hku.hken_HK
dc.identifier.authorityKwong, YL=rp00358en_HK
dc.identifier.authorityLiang, RHS=rp00345en_HK
dc.identifier.authoritySrivastava, G=rp00365en_HK
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1002/path.2699en_HK
dc.identifier.pmid20235165-
dc.identifier.scopuseid_2-s2.0-77952769635en_HK
dc.identifier.hkuros176920-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77952769635&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume221en_HK
dc.identifier.issue2en_HK
dc.identifier.spage164en_HK
dc.identifier.epage174en_HK
dc.identifier.eissn1096-9896-
dc.identifier.isiWOS:000278209800006-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridChan, KK=8986914100en_HK
dc.identifier.scopusauthoridShen, L=7401704659en_HK
dc.identifier.scopusauthoridAu, WY=7202383089en_HK
dc.identifier.scopusauthoridYuen, HF=14018633400en_HK
dc.identifier.scopusauthoridWong, KY=7404758500en_HK
dc.identifier.scopusauthoridGuo, T=16743820700en_HK
dc.identifier.scopusauthoridWong, MLY=37021112700en_HK
dc.identifier.scopusauthoridShimizu, N=7403575308en_HK
dc.identifier.scopusauthoridTsuchiyama, J=6701325733en_HK
dc.identifier.scopusauthoridKwong, YL=7102818954en_HK
dc.identifier.scopusauthoridLiang, RHS=26643224900en_HK
dc.identifier.scopusauthoridSrivastava, G=7202242238en_HK

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