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Article: Interleukin-2 induces NF-κB activation through BCL10 and affects its subcellular localization in natural killer lymphoma cells
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TitleInterleukin-2 induces NF-κB activation through BCL10 and affects its subcellular localization in natural killer lymphoma cells
 
AuthorsChan, KK1
Shen, L1
Au, WY1
Yuen, HF1
Wong, KY1
Guo, T1
Wong, MLY1
Shimizu, N2
Tsuchiyama, J3
Kwong, YL1
Liang, RHS1
Srivastava, G1
 
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
 
CitationJournal Of Pathology, 2010, v. 221 n. 2, p. 164-174 [How to Cite?]
DOI: http://dx.doi.org/10.1002/path.2699
 
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.
 
ISSN0022-3417
2013 Impact Factor: 7.330
 
DOIhttp://dx.doi.org/10.1002/path.2699
 
ISI Accession Number IDWOS:000278209800006
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).

 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorChan, KK
 
dc.contributor.authorShen, L
 
dc.contributor.authorAu, WY
 
dc.contributor.authorYuen, HF
 
dc.contributor.authorWong, KY
 
dc.contributor.authorGuo, T
 
dc.contributor.authorWong, MLY
 
dc.contributor.authorShimizu, N
 
dc.contributor.authorTsuchiyama, J
 
dc.contributor.authorKwong, YL
 
dc.contributor.authorLiang, RHS
 
dc.contributor.authorSrivastava, G
 
dc.date.accessioned2012-05-29T06:14:09Z
 
dc.date.available2012-05-29T06:14:09Z
 
dc.date.issued2010
 
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.
 
dc.description.naturelink_to_subscribed_fulltext
 
dc.identifier.citationJournal Of Pathology, 2010, v. 221 n. 2, p. 164-174 [How to Cite?]
DOI: http://dx.doi.org/10.1002/path.2699
 
dc.identifier.doihttp://dx.doi.org/10.1002/path.2699
 
dc.identifier.eissn1096-9896
 
dc.identifier.epage174
 
dc.identifier.hkuros176920
 
dc.identifier.isiWOS:000278209800006
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).

 
dc.identifier.issn0022-3417
2013 Impact Factor: 7.330
 
dc.identifier.issue2
 
dc.identifier.pmid20235165
 
dc.identifier.scopuseid_2-s2.0-77952769635
 
dc.identifier.spage164
 
dc.identifier.urihttp://hdl.handle.net/10722/148621
 
dc.identifier.volume221
 
dc.languageeng
 
dc.publisherJohn Wiley & Sons. The Journal's web site is located at http://www3.interscience.wiley.com/cgi-bin/jhome/1130
 
dc.publisher.placeUnited Kingdom
 
dc.relation.ispartofJournal of Pathology
 
dc.relation.referencesReferences in Scopus
 
dc.subject.meshAdaptor Proteins, Signal Transducing - Genetics - Metabolism
 
dc.subject.meshCell Line
 
dc.subject.meshCell Nucleus - Metabolism
 
dc.subject.meshGene Expression Regulation - Genetics
 
dc.subject.meshHumans
 
dc.subject.meshInterleukin-2 - Pharmacology - Physiology
 
dc.subject.meshLymphoma, Extranodal Nk-T-Cell - Metabolism
 
dc.subject.meshNf-Kappa B - Genetics - Metabolism
 
dc.subject.meshProto-Oncogene Proteins - Metabolism
 
dc.subject.meshProto-Oncogene Proteins C-Akt - Metabolism
 
dc.subject.meshSignal Transduction - Genetics
 
dc.subject.meshTranscription Factors - Metabolism
 
dc.subjectB
 
dc.subjectBCL10
 
dc.subjectIL2
 
dc.subjectNF-κ
 
dc.subjectNK cell lymphoma
 
dc.subjectNucleus
 
dc.titleInterleukin-2 induces NF-κB activation through BCL10 and affects its subcellular localization in natural killer lymphoma cells
 
dc.typeArticle
 
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<description.abstract>Deregulation of nuclear factor (NF)-&#954;B signalling is common in cancers and is essential for tumourigenesis. Constitutive NF-&#954;B 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-&#954;B 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-&#954;B activation and BCL10 subcellular localization in ENKLs. In the present study, IL2-activated NK lymphoma cells were found to induce NF-&#954;B activation via the PI3K/Akt pathway, leading to an increase in the entry of G 2/M phase and concomitant transcription of NF-&#954;B-responsive genes. We also found that BCL10, a key mediator of NF-&#954;B signalling, participates in the cytokine receptor-induced activation of NF-&#954;B. Knockdown of BCL10 expression resulted in deficient NF-&#954;B signalling, whereas Akt activation was unaffected. Our results suggest that BCL10 plays a role downstream of Akt in the IL2-triggered NF-&#954;B 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-&#954;B 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-&#954;B signalling pathway that promotes the pathogenesis of NK cell lymphomas. Copyright &#169; 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.</description.abstract>
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Author Affiliations
  1. The University of Hong Kong
  2. Tokyo Medical and Dental University
  3. Kawasaki Medical College