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Article: Proteasome mediated degradation of Id-1 is associated with TNFα-induced apoptosis in prostate cancer cells

TitleProteasome mediated degradation of Id-1 is associated with TNFα-induced apoptosis in prostate cancer cells
Authors
Issue Date2006
PublisherOxford University Press. The Journal's web site is located at http://carcin.oxfordjournals.org/
Citation
Carcinogenesis, 2006, v. 27 n. 2, p. 205-215 How to Cite?
AbstractOverexpression of the helix-loop-helix protein Id-1 has been reported in over 20 types of cancer. While a number of factors have been demonstrated to regulate Id-1 gene transcription, little is known about the mechanisms responsible for its degradation. In this study, we have demonstrated that Id-1 protein stability was regulated by TNFα in prostate cancer cells. We found that exposure of prostate cancer cell lines, DU145 and PC-3, to TNFα resulted in a rapid and significant downregulation of the Id-1 protein level. The fact that neither the Id-1 promoter activity nor the Id-1 mRNA level was affected by the TNFα treatment suggested that the decrease in Id-1 protein was not due to the suppression of gene transcription. In addition, the half-life of the Id-1 protein was decreased in both cell lines in the presence of TNFα, and the addition of an ubiquitin/proteasome inhibitor (MG-132) prior to the TNFα treatment completely blocked the effect of the TNFα-induced Id-1 protein degradation. Furthermore, introduction of a Flag-tag sequence into the N-terminus region of the Id-1 protein, which has been shown to stabilize the protein, was able to protect the Id-1 protein from TNFα-induced degradation. These results suggest that TNFα downregulated Id-1 through activation of the ubiquitin/proteasome degradation pathway in prostate cancer cells. Interestingly, in both DU145 and PC-3 cells, the decrease of Id-1 protein was associated with the activation of apoptotic pathway, as evidenced by the increased expression of cleaved PARP and caspase 3. In addition, TNFα failed to downregulate Id-1 in a sub-line of LNCaP cells that was resistant to TNFα-induced apoptosis. These results further suggest that the downregulation of Id-1 may facilitate TNFα-induced apoptosis in prostate cancer cells. In conclusion, our findings indicate that Id-1 protein may be regulated by TNFα through the ubiquitin/proteasome degradation pathway and the stability of the Id-1 protein appears to correlate with the sensitivity of TNFα-induced apoptosis. © Oxford University Press 2005; all rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/149648
ISSN
2015 Impact Factor: 4.874
2015 SCImago Journal Rankings: 2.439
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorLing, MTen_US
dc.contributor.authorKwok, WKen_US
dc.contributor.authorFung, MKen_US
dc.contributor.authorXianghong, Wen_US
dc.contributor.authorWong, YCen_US
dc.date.accessioned2012-06-26T05:56:30Z-
dc.date.available2012-06-26T05:56:30Z-
dc.date.issued2006en_US
dc.identifier.citationCarcinogenesis, 2006, v. 27 n. 2, p. 205-215en_US
dc.identifier.issn0143-3334en_US
dc.identifier.urihttp://hdl.handle.net/10722/149648-
dc.description.abstractOverexpression of the helix-loop-helix protein Id-1 has been reported in over 20 types of cancer. While a number of factors have been demonstrated to regulate Id-1 gene transcription, little is known about the mechanisms responsible for its degradation. In this study, we have demonstrated that Id-1 protein stability was regulated by TNFα in prostate cancer cells. We found that exposure of prostate cancer cell lines, DU145 and PC-3, to TNFα resulted in a rapid and significant downregulation of the Id-1 protein level. The fact that neither the Id-1 promoter activity nor the Id-1 mRNA level was affected by the TNFα treatment suggested that the decrease in Id-1 protein was not due to the suppression of gene transcription. In addition, the half-life of the Id-1 protein was decreased in both cell lines in the presence of TNFα, and the addition of an ubiquitin/proteasome inhibitor (MG-132) prior to the TNFα treatment completely blocked the effect of the TNFα-induced Id-1 protein degradation. Furthermore, introduction of a Flag-tag sequence into the N-terminus region of the Id-1 protein, which has been shown to stabilize the protein, was able to protect the Id-1 protein from TNFα-induced degradation. These results suggest that TNFα downregulated Id-1 through activation of the ubiquitin/proteasome degradation pathway in prostate cancer cells. Interestingly, in both DU145 and PC-3 cells, the decrease of Id-1 protein was associated with the activation of apoptotic pathway, as evidenced by the increased expression of cleaved PARP and caspase 3. In addition, TNFα failed to downregulate Id-1 in a sub-line of LNCaP cells that was resistant to TNFα-induced apoptosis. These results further suggest that the downregulation of Id-1 may facilitate TNFα-induced apoptosis in prostate cancer cells. In conclusion, our findings indicate that Id-1 protein may be regulated by TNFα through the ubiquitin/proteasome degradation pathway and the stability of the Id-1 protein appears to correlate with the sensitivity of TNFα-induced apoptosis. © Oxford University Press 2005; all rights reserved.en_US
dc.languageengen_US
dc.publisherOxford University Press. The Journal's web site is located at http://carcin.oxfordjournals.org/en_US
dc.relation.ispartofCarcinogenesisen_US
dc.subject.meshApoptosisen_US
dc.subject.meshCell Line, Tumoren_US
dc.subject.meshDown-Regulationen_US
dc.subject.meshHalf-Lifeen_US
dc.subject.meshHumansen_US
dc.subject.meshInhibitor Of Differentiation Protein 1 - Biosynthesis - Metabolismen_US
dc.subject.meshMaleen_US
dc.subject.meshProstatic Neoplasms - Genetics - Pathologyen_US
dc.subject.meshProteasome Endopeptidase Complexen_US
dc.subject.meshRna, Messenger - Analysis - Biosynthesisen_US
dc.subject.meshTumor Necrosis Factor-Alpha - Physiologyen_US
dc.subject.meshUbiquitinen_US
dc.titleProteasome mediated degradation of Id-1 is associated with TNFα-induced apoptosis in prostate cancer cellsen_US
dc.typeArticleen_US
dc.identifier.emailLing, MT:patling@hkucc.hku.hken_US
dc.identifier.emailWong, YC:ycwong@hkucc.hku.hken_US
dc.identifier.authorityLing, MT=rp00449en_US
dc.identifier.authorityWong, YC=rp00316en_US
dc.description.naturelink_to_OA_fulltexten_US
dc.identifier.doi10.1093/carcin/bgi217en_US
dc.identifier.pmid16123120-
dc.identifier.scopuseid_2-s2.0-31544475135en_US
dc.identifier.hkuros113700-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-31544475135&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume27en_US
dc.identifier.issue2en_US
dc.identifier.spage205en_US
dc.identifier.epage215en_US
dc.identifier.isiWOS:000234778700003-
dc.publisher.placeUnited Kingdomen_US
dc.identifier.scopusauthoridLing, MT=7102229780en_US
dc.identifier.scopusauthoridKwok, WK=8578541800en_US
dc.identifier.scopusauthoridFung, MK=8718040400en_US
dc.identifier.scopusauthoridXianghong, W=24480009900en_US
dc.identifier.scopusauthoridWong, YC=7403041798en_US
dc.identifier.citeulike479804-

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