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- Publisher Website: 10.1002/path.2699
- Scopus: eid_2-s2.0-77952769635
- PMID: 20235165
- WOS: WOS:000278209800006
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Article: Interleukin-2 induces NF-κB activation through BCL10 and affects its subcellular localization in natural killer lymphoma cells
Title | Interleukin-2 induces NF-κB activation through BCL10 and affects its subcellular localization in natural killer lymphoma cells | ||||
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Authors | |||||
Keywords | B BCL10 IL2 NF-κ NK cell lymphoma Nucleus | ||||
Issue Date | 2010 | ||||
Publisher | John 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? | ||||
Abstract | Deregulation 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 Identifier | http://hdl.handle.net/10722/148621 | ||||
ISSN | 2023 Impact Factor: 5.6 2023 SCImago Journal Rankings: 2.426 | ||||
ISI Accession Number ID |
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 Field | Value | Language |
---|---|---|
dc.contributor.author | Chan, KK | en_HK |
dc.contributor.author | Shen, L | en_HK |
dc.contributor.author | Au, WY | en_HK |
dc.contributor.author | Yuen, HF | en_HK |
dc.contributor.author | Wong, KY | en_HK |
dc.contributor.author | Guo, T | en_HK |
dc.contributor.author | Wong, MLY | en_HK |
dc.contributor.author | Shimizu, N | en_HK |
dc.contributor.author | Tsuchiyama, J | en_HK |
dc.contributor.author | Kwong, YL | en_HK |
dc.contributor.author | Liang, RHS | en_HK |
dc.contributor.author | Srivastava, G | en_HK |
dc.date.accessioned | 2012-05-29T06:14:09Z | - |
dc.date.available | 2012-05-29T06:14:09Z | - |
dc.date.issued | 2010 | en_HK |
dc.identifier.citation | Journal Of Pathology, 2010, v. 221 n. 2, p. 164-174 | en_HK |
dc.identifier.issn | 0022-3417 | en_HK |
dc.identifier.uri | http://hdl.handle.net/10722/148621 | - |
dc.description.abstract | Deregulation 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.language | eng | en_US |
dc.publisher | John Wiley & Sons. The Journal's web site is located at http://www3.interscience.wiley.com/cgi-bin/jhome/1130 | en_HK |
dc.relation.ispartof | Journal of Pathology | en_HK |
dc.subject | B | en_HK |
dc.subject | BCL10 | en_HK |
dc.subject | IL2 | en_HK |
dc.subject | NF-κ | en_HK |
dc.subject | NK cell lymphoma | en_HK |
dc.subject | Nucleus | en_HK |
dc.subject.mesh | Adaptor Proteins, Signal Transducing - Genetics - Metabolism | en_US |
dc.subject.mesh | Cell Line | en_US |
dc.subject.mesh | Cell Nucleus - Metabolism | en_US |
dc.subject.mesh | Gene Expression Regulation - Genetics | en_US |
dc.subject.mesh | Humans | en_US |
dc.subject.mesh | Interleukin-2 - Pharmacology - Physiology | en_US |
dc.subject.mesh | Lymphoma, Extranodal Nk-T-Cell - Metabolism | en_US |
dc.subject.mesh | Nf-Kappa B - Genetics - Metabolism | en_US |
dc.subject.mesh | Proto-Oncogene Proteins - Metabolism | en_US |
dc.subject.mesh | Proto-Oncogene Proteins C-Akt - Metabolism | en_US |
dc.subject.mesh | Signal Transduction - Genetics | en_US |
dc.subject.mesh | Transcription Factors - Metabolism | en_US |
dc.title | Interleukin-2 induces NF-κB activation through BCL10 and affects its subcellular localization in natural killer lymphoma cells | en_HK |
dc.type | Article | en_HK |
dc.identifier.email | Kwong, YL:ylkwong@hku.hk | en_HK |
dc.identifier.email | Liang, RHS:rliang@hku.hk | en_HK |
dc.identifier.email | Srivastava, G:gopesh@pathology.hku.hk | en_HK |
dc.identifier.authority | Kwong, YL=rp00358 | en_HK |
dc.identifier.authority | Liang, RHS=rp00345 | en_HK |
dc.identifier.authority | Srivastava, G=rp00365 | en_HK |
dc.description.nature | link_to_subscribed_fulltext | en_US |
dc.identifier.doi | 10.1002/path.2699 | en_HK |
dc.identifier.pmid | 20235165 | - |
dc.identifier.scopus | eid_2-s2.0-77952769635 | en_HK |
dc.identifier.hkuros | 176920 | - |
dc.relation.references | http://www.scopus.com/mlt/select.url?eid=2-s2.0-77952769635&selection=ref&src=s&origin=recordpage | en_HK |
dc.identifier.volume | 221 | en_HK |
dc.identifier.issue | 2 | en_HK |
dc.identifier.spage | 164 | en_HK |
dc.identifier.epage | 174 | en_HK |
dc.identifier.eissn | 1096-9896 | - |
dc.identifier.isi | WOS:000278209800006 | - |
dc.publisher.place | United Kingdom | en_HK |
dc.identifier.scopusauthorid | Chan, KK=8986914100 | en_HK |
dc.identifier.scopusauthorid | Shen, L=7401704659 | en_HK |
dc.identifier.scopusauthorid | Au, WY=7202383089 | en_HK |
dc.identifier.scopusauthorid | Yuen, HF=14018633400 | en_HK |
dc.identifier.scopusauthorid | Wong, KY=7404758500 | en_HK |
dc.identifier.scopusauthorid | Guo, T=16743820700 | en_HK |
dc.identifier.scopusauthorid | Wong, MLY=37021112700 | en_HK |
dc.identifier.scopusauthorid | Shimizu, N=7403575308 | en_HK |
dc.identifier.scopusauthorid | Tsuchiyama, J=6701325733 | en_HK |
dc.identifier.scopusauthorid | Kwong, YL=7102818954 | en_HK |
dc.identifier.scopusauthorid | Liang, RHS=26643224900 | en_HK |
dc.identifier.scopusauthorid | Srivastava, G=7202242238 | en_HK |
dc.identifier.issnl | 0022-3417 | - |