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Conference Paper: Proteasome mediated degradation of Id-1 is associated with TNF-alpha induced apoptosis in prostate cancer cells

TitleProteasome mediated degradation of Id-1 is associated with TNF-alpha induced apoptosis in prostate cancer cells
Authors
Issue Date2005
PublisherAmerican Association for Cancer Research
Citation
AACR 96th Annual Meeting, Anaheim CA, 16–20 April 2005. In Cancer Research, 2005, v. 65 n. 9S, p. 1267 Abstract no. 5365 How to Cite?
AbstractOverexpression of the he Helix-loop-helix protein Id-1 has been reported in over 20 types of cancer and recent study suggested that, in addition to its effect on cell growth and differentiation, Id-1 also involves in regulation of apoptosis. Previously, we have reported that suppression of Id-1 expression, which leads to downregulation of NF-KappaB activities, resulted in sensitization of the androgen independent prostate cancer cell to TNF-α induced apoptosis. In this study, we have shown that exposure of the androgen independent prostate cancer cells to TNF-α resulted in rapid and significant downregulation of the Id-1 protein level. The decrease in Id-1 expression is not due to decrease in gene transcription, since Id-1 promoter activities as well as the Id-1 mRNA level was not affected by the TNF-α treatment. Instead, the half-life of the Id-1 protein was decreased in both cell lines in the presence of TNF-α, and the addition of the proteasome inhibitor prior to the TNF-α treatment completely abolished the effect of the TNF-α on Id-1 protein. In addition, introduction of a Flag-tag epitode into the N-terminus of the Id-1, which has been shown to protect the protein from proteasome induced degradation, confer the protein resistance to the TNF-α treatment, suggesting that TNF-α induced the degradation of the Id-1 protein through activation of the proteosome degradation pathway in prostate cancer cells. Interestingly, while the two cell lines were initially resistant to TNF-α, prolong treatment of the cell result in initiation of apoptosis which coincided with disappear of the Id-1 protein, suggesting that Id-1 level correlates with the response of the cell to TNF-α induced apoptosis. This was further support by the finding that Id-1 protein are relatively more stable in the late passage of the LNCaP cells, which was also more resistant to the TNF-α induced apoptosis, than in the early passage. In conclusion, our finding indicated that Id-1 protein is regulated by TNF-α through the proteasome degradation pathway and the stability of the Id-1 protein appears to correlate with the sensitivity of the cells toward TNF-α induced apoptosis.
Persistent Identifierhttp://hdl.handle.net/10722/95009
ISSN
2015 Impact Factor: 8.556
2015 SCImago Journal Rankings: 5.372

 

DC FieldValueLanguage
dc.contributor.authorLing, MTen_HK
dc.contributor.authorFung, KLen_HK
dc.contributor.authorWang, Xen_HK
dc.contributor.authorWong, YCen_HK
dc.date.accessioned2010-09-25T15:48:48Z-
dc.date.available2010-09-25T15:48:48Z-
dc.date.issued2005en_HK
dc.identifier.citationAACR 96th Annual Meeting, Anaheim CA, 16–20 April 2005. In Cancer Research, 2005, v. 65 n. 9S, p. 1267 Abstract no. 5365en_HK
dc.identifier.issn0008-5472-
dc.identifier.urihttp://hdl.handle.net/10722/95009-
dc.description.abstractOverexpression of the he Helix-loop-helix protein Id-1 has been reported in over 20 types of cancer and recent study suggested that, in addition to its effect on cell growth and differentiation, Id-1 also involves in regulation of apoptosis. Previously, we have reported that suppression of Id-1 expression, which leads to downregulation of NF-KappaB activities, resulted in sensitization of the androgen independent prostate cancer cell to TNF-α induced apoptosis. In this study, we have shown that exposure of the androgen independent prostate cancer cells to TNF-α resulted in rapid and significant downregulation of the Id-1 protein level. The decrease in Id-1 expression is not due to decrease in gene transcription, since Id-1 promoter activities as well as the Id-1 mRNA level was not affected by the TNF-α treatment. Instead, the half-life of the Id-1 protein was decreased in both cell lines in the presence of TNF-α, and the addition of the proteasome inhibitor prior to the TNF-α treatment completely abolished the effect of the TNF-α on Id-1 protein. In addition, introduction of a Flag-tag epitode into the N-terminus of the Id-1, which has been shown to protect the protein from proteasome induced degradation, confer the protein resistance to the TNF-α treatment, suggesting that TNF-α induced the degradation of the Id-1 protein through activation of the proteosome degradation pathway in prostate cancer cells. Interestingly, while the two cell lines were initially resistant to TNF-α, prolong treatment of the cell result in initiation of apoptosis which coincided with disappear of the Id-1 protein, suggesting that Id-1 level correlates with the response of the cell to TNF-α induced apoptosis. This was further support by the finding that Id-1 protein are relatively more stable in the late passage of the LNCaP cells, which was also more resistant to the TNF-α induced apoptosis, than in the early passage. In conclusion, our finding indicated that Id-1 protein is regulated by TNF-α through the proteasome degradation pathway and the stability of the Id-1 protein appears to correlate with the sensitivity of the cells toward TNF-α induced apoptosis.-
dc.languageengen_HK
dc.publisherAmerican Association for Cancer Research-
dc.relation.ispartofCancer Researchen_HK
dc.titleProteasome mediated degradation of Id-1 is associated with TNF-alpha induced apoptosis in prostate cancer cellsen_HK
dc.typeConference_Paperen_HK
dc.identifier.emailLing, MT: patling@HKUCC.hku.hken_HK
dc.identifier.emailWong, YC: ycwong@hkucc.hku.hken_HK
dc.identifier.authorityLing, MT=rp00449en_HK
dc.identifier.authorityWong, YC=rp00316en_HK
dc.identifier.hkuros98015en_HK
dc.identifier.volume65en_HK
dc.identifier.spage1267en_HK

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