NUB1, an interferon-inducible protein, mediates anti-proliferative actions and apoptosis in renal cell carcinoma cells through cell-cycle regulation.

Hdl Handle:
http://hdl.handle.net/10675.2/29
Title:
NUB1, an interferon-inducible protein, mediates anti-proliferative actions and apoptosis in renal cell carcinoma cells through cell-cycle regulation.
Authors:
Hosono, T; Tanaka, Tomoaki; Tanji, K; Nakatani, T; Kamitani, Tetsu
Abstract:
BACKGROUND: NEDD8 ultimate buster 1 (NUB1) is an interferon (IFN)-inducible protein that downregulates NEDD8 expression and its conjugation system. Although overexpression of NUB1 induces a growth-inhibitory effect in cells, the mechanisms underlying the anti-mitogenic actions of NUB1 in cancer cells remain uncertain. We investigated the anti-cancer effects of NUB1 in human renal cell carcinoma (RCC) cells. METHODS: Nine human RCC cells were used for this study. The proliferation of RCC cells exposed to IFN-alpha was measured by water-soluble tetrazolium salt assay. The expression level of NUB1 in cells was measured by quantitative reverse transcriptase PCR or western blot analysis. Apoptosis and cell-cycle analysis were performed by flow cytometry. Silencing of NUB1 was performed using a small interfering RNA. RESULTS: Both NUB1 messenger RNA and protein were significantly induced by IFN-alpha in seven out of nine selected RCC cell lines, and the NUB1 expressions induced by IFN-alpha correlated positively with cell growth inhibition. Overexpression of NUB1 remarkably induced S-phase transition during cell cycle and apoptosis in IFN-alpha-resistant A498 cells, in which NUB1 is not induced by IFN-alpha. The expression levels of two cell-cycle regulator proteins, cyclin E and p27, were increased under the aforementioned conditions. The knockdown of NUB1 enhanced cell proliferation of IFN-alpha-resistant A498 cells and suppressed IFN-alpha-induced growth inhibition in IFN-alpha-sensitive 4TUHR cells. CONCLUSION: NUB1 may be a key factor involved not only in cell growth inhibition by IFN-alpha in RCC cells but also in the anti-cancer effect against IFN-alpha-resistant RCC cells.
Citation:
Br J Cancer. 2010 Mar 2; 102(5):873-882
Issue Date:
3-Mar-2010
URI:
http://hdl.handle.net/10675.2/29
DOI:
10.1038/sj.bjc.6605574
PubMed ID:
20160729
PubMed Central ID:
PMC2833260
Type:
Journal Article; Research Support, Non-U.S. Gov't
ISSN:
1532-1827
Appears in Collections:
Center for Molecular Chaperone/Radiobiology & Cancer Virology: Faculty Research and Presentations

Full metadata record

DC FieldValue Language
dc.contributor.authorHosono, Ten_US
dc.contributor.authorTanaka, Tomoakien_US
dc.contributor.authorTanji, Ken_US
dc.contributor.authorNakatani, Ten_US
dc.contributor.authorKamitani, Tetsuen_US
dc.date.accessioned2010-09-24T21:05:58Z-
dc.date.available2010-09-24T21:05:58Z-
dc.date.issued2010-03-03en_US
dc.identifier.citationBr J Cancer. 2010 Mar 2; 102(5):873-882en_US
dc.identifier.issn1532-1827en_US
dc.identifier.pmid20160729en_US
dc.identifier.doi10.1038/sj.bjc.6605574en_US
dc.identifier.urihttp://hdl.handle.net/10675.2/29-
dc.description.abstractBACKGROUND: NEDD8 ultimate buster 1 (NUB1) is an interferon (IFN)-inducible protein that downregulates NEDD8 expression and its conjugation system. Although overexpression of NUB1 induces a growth-inhibitory effect in cells, the mechanisms underlying the anti-mitogenic actions of NUB1 in cancer cells remain uncertain. We investigated the anti-cancer effects of NUB1 in human renal cell carcinoma (RCC) cells. METHODS: Nine human RCC cells were used for this study. The proliferation of RCC cells exposed to IFN-alpha was measured by water-soluble tetrazolium salt assay. The expression level of NUB1 in cells was measured by quantitative reverse transcriptase PCR or western blot analysis. Apoptosis and cell-cycle analysis were performed by flow cytometry. Silencing of NUB1 was performed using a small interfering RNA. RESULTS: Both NUB1 messenger RNA and protein were significantly induced by IFN-alpha in seven out of nine selected RCC cell lines, and the NUB1 expressions induced by IFN-alpha correlated positively with cell growth inhibition. Overexpression of NUB1 remarkably induced S-phase transition during cell cycle and apoptosis in IFN-alpha-resistant A498 cells, in which NUB1 is not induced by IFN-alpha. The expression levels of two cell-cycle regulator proteins, cyclin E and p27, were increased under the aforementioned conditions. The knockdown of NUB1 enhanced cell proliferation of IFN-alpha-resistant A498 cells and suppressed IFN-alpha-induced growth inhibition in IFN-alpha-sensitive 4TUHR cells. CONCLUSION: NUB1 may be a key factor involved not only in cell growth inhibition by IFN-alpha in RCC cells but also in the anti-cancer effect against IFN-alpha-resistant RCC cells.en_US
dc.rightsThe PMC Open Access Subset is a relatively small part of the total collection of articles in PMC. Articles in the PMC Open Access Subset are still protected by copyright, but are made available under a Creative Commons or similar license that generally allows more liberal redistribution and reuse than a traditional copyrighted work. Please refer to the license statement in each article for specific terms of use. The license terms are not identical for all articles in this subset.en_US
dc.subject.meshApoptosisen_US
dc.subject.meshBlotting, Westernen_US
dc.subject.meshCarcinoma, Renal Cell / drug therapy / metabolism / pathologyen_US
dc.subject.meshCell Line, Tumoren_US
dc.subject.meshCell Proliferationen_US
dc.subject.meshCyclin E / genetics / metabolismen_US
dc.subject.meshCyclin-Dependent Kinase Inhibitor p27 / genetics / metabolismen_US
dc.subject.meshHumansen_US
dc.subject.meshInterferon-alpha / pharmacologyen_US
dc.subject.meshKidney Neoplasms / drug therapy / metabolism / pathologyen_US
dc.subject.meshOncogene Proteins / genetics / metabolismen_US
dc.subject.meshRNA, Messenger / genetics / metabolismen_US
dc.subject.meshRNA, Small Interfering / pharmacologyen_US
dc.subject.meshReverse Transcriptase Polymerase Chain Reactionen_US
dc.subject.meshS Phaseen_US
dc.subject.meshTranscription Factors / antagonists & inhibitors / genetics / metabolismen_US
dc.titleNUB1, an interferon-inducible protein, mediates anti-proliferative actions and apoptosis in renal cell carcinoma cells through cell-cycle regulation.en_US
dc.typeJournal Articleen_US
dc.typeResearch Support, Non-U.S. Gov'ten_US
dc.identifier.pmcidPMC2833260en_US
dc.contributor.corporatenameCenter for Molecular Chaperone/Radiobiology & Cancer Virologyen_US

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