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Article: Chromodomain helicase/adenosine triphosphatase DNA binding protein 1-like (CHD1L) gene suppresses the nucleus-to-mitochondria translocation of Nur77 to sustain hepatocellular carcinoma cell survival

TitleChromodomain helicase/adenosine triphosphatase DNA binding protein 1-like (CHD1L) gene suppresses the nucleus-to-mitochondria translocation of Nur77 to sustain hepatocellular carcinoma cell survival
Authors
Issue Date2009
PublisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www.hepatology.org/
Citation
Hepatology, 2009, v. 50 n. 1, p. 122-129 How to Cite?
AbstractAmplification of 1q21 has been detected in 58% to 78% of primary hepatocellular carcinoma cases, suggesting that one or more oncogenes within the amplicon play a critical role in the development of this disease. The chromodomain helicase/adenosine triphosphatase DNA binding protein 1-like gene (CHD1L) is a recently identified oncogene localized at 1q21. Our previous studies have demonstrated that CHD1L has strong tumorigenic ability and confers high susceptibility to spontaneous tumors in a CHD1L-transgenic mouse model. In this study, we demonstrate that the antiapoptotic ability of CHD1L is associated with its interaction with Nur77, a critical member of a p53-independent apoptotic pathway. As the first cellular protein identified to bind Nur77, CHD1L is able to inhibit the nucleus-to-mitochondria translocation of Nur77, which is the key step of Nur77-mediated apoptosis, resulting in the hindrance of the release of cytochrome c and the initiation of apoptosis. Knock-down of CHD1L expression by RNA interference could rescue the mitochondrial targeting of Nur77 and the subsequent apoptosis. Further studies found that the C-terminal Macro domain of CHD1L is responsible for the interaction with Nur77, and a CHD1L mutant lacking residues 600-897 failed to interact with Nur77 and prevented Nur77-mediated apoptosis. More importantly, we found that the inhibition of Nur77-mediated apoptosis by endogenous CHD1L is a critical biological cellular process in hepatocarcinogenesis. Conclusion: We demonstrate in this study that overexpression of CHD1L could sustain tumor cell survival by preventing Nur77-mediated apoptosis. © 2009 by the American Association for the Study of Liver Diseases.
Persistent Identifierhttp://hdl.handle.net/10722/58204
ISSN
2015 Impact Factor: 11.711
2015 SCImago Journal Rankings: 4.752
ISI Accession Number ID
Funding AgencyGrant Number
Hong Kong Research Grant CouncilHKU 7393/04M
HKU I/106C
Sun Yat-Sen University85000-3171311
Major State Basic Research Program of China2006CB910104
Foundation of Guangzhou Science and Technology Bureau2005Z1-E01301
Funding Information:

Supported by Hong Kong Research Grant Council Grant HKU 7393/04M, Hong Kong Research Grant Council Central Allocation HKU I/106C, the "Hundred 7 dents Program" at Sun Yat-Sen University (85000-3171311), the Major State Basic Research Program of China (2006CB910104), and a grant from the Foundation of Guangzhou Science and Technology Bureau (2005Z1-E01301).

References
Grants

 

DC FieldValueLanguage
dc.contributor.authorChen, Len_HK
dc.contributor.authorHu, Len_HK
dc.contributor.authorChan, THMen_HK
dc.contributor.authorTsao, GSWen_HK
dc.contributor.authorXie, Den_HK
dc.contributor.authorHuo, KKen_HK
dc.contributor.authorFu, Len_HK
dc.contributor.authorMa, Sen_HK
dc.contributor.authorZheng, BJen_HK
dc.contributor.authorGuan, XYen_HK
dc.date.accessioned2010-05-31T03:25:47Z-
dc.date.available2010-05-31T03:25:47Z-
dc.date.issued2009en_HK
dc.identifier.citationHepatology, 2009, v. 50 n. 1, p. 122-129en_HK
dc.identifier.issn0270-9139en_HK
dc.identifier.urihttp://hdl.handle.net/10722/58204-
dc.description.abstractAmplification of 1q21 has been detected in 58% to 78% of primary hepatocellular carcinoma cases, suggesting that one or more oncogenes within the amplicon play a critical role in the development of this disease. The chromodomain helicase/adenosine triphosphatase DNA binding protein 1-like gene (CHD1L) is a recently identified oncogene localized at 1q21. Our previous studies have demonstrated that CHD1L has strong tumorigenic ability and confers high susceptibility to spontaneous tumors in a CHD1L-transgenic mouse model. In this study, we demonstrate that the antiapoptotic ability of CHD1L is associated with its interaction with Nur77, a critical member of a p53-independent apoptotic pathway. As the first cellular protein identified to bind Nur77, CHD1L is able to inhibit the nucleus-to-mitochondria translocation of Nur77, which is the key step of Nur77-mediated apoptosis, resulting in the hindrance of the release of cytochrome c and the initiation of apoptosis. Knock-down of CHD1L expression by RNA interference could rescue the mitochondrial targeting of Nur77 and the subsequent apoptosis. Further studies found that the C-terminal Macro domain of CHD1L is responsible for the interaction with Nur77, and a CHD1L mutant lacking residues 600-897 failed to interact with Nur77 and prevented Nur77-mediated apoptosis. More importantly, we found that the inhibition of Nur77-mediated apoptosis by endogenous CHD1L is a critical biological cellular process in hepatocarcinogenesis. Conclusion: We demonstrate in this study that overexpression of CHD1L could sustain tumor cell survival by preventing Nur77-mediated apoptosis. © 2009 by the American Association for the Study of Liver Diseases.en_HK
dc.languageengen_HK
dc.publisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www.hepatology.org/en_HK
dc.relation.ispartofHepatologyen_HK
dc.rightsHepatology. Copyright © John Wiley & Sons, Inc.en_HK
dc.titleChromodomain helicase/adenosine triphosphatase DNA binding protein 1-like (CHD1L) gene suppresses the nucleus-to-mitochondria translocation of Nur77 to sustain hepatocellular carcinoma cell survivalen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0270-9139&volume=50&spage=122&epage=129&date=2009&atitle=Chromodomain+helicase/adenosine+triphosphatase+DNA+binding+protein+1-like+(CHD1l)+gene+suppresses+the+nucleus-to-mitochondria+translocation+of+nur77+to+sustain+hepatocellular+carcinoma+cell+survival.en_HK
dc.identifier.emailTsao, GSW:gswtsao@hkucc.hku.hken_HK
dc.identifier.emailFu, L:gracelfu@hku.hken_HK
dc.identifier.emailMa, S:sma@pathology.hku.hken_HK
dc.identifier.emailZheng, BJ:bzheng@hkucc.hku.hken_HK
dc.identifier.emailGuan, XY:xyguan@hkucc.hku.hken_HK
dc.identifier.authorityTsao, GSW=rp00399en_HK
dc.identifier.authorityFu, L=rp01435en_HK
dc.identifier.authorityMa, S=rp00506en_HK
dc.identifier.authorityZheng, BJ=rp00353en_HK
dc.identifier.authorityGuan, XY=rp00454en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1002/hep.22933en_HK
dc.identifier.scopuseid_2-s2.0-67651174841en_HK
dc.identifier.hkuros157421en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-67651174841&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume50en_HK
dc.identifier.issue1en_HK
dc.identifier.spage122en_HK
dc.identifier.epage129en_HK
dc.identifier.isiWOS:000267605500015-
dc.publisher.placeUnited Statesen_HK
dc.relation.projectCharacterization of roles of a novel oncogene ALC-1 in the development of hepatocellular carcinoma-
dc.identifier.scopusauthoridChen, L=23569135400en_HK
dc.identifier.scopusauthoridHu, L=34770075600en_HK
dc.identifier.scopusauthoridChan, THM=26431726400en_HK
dc.identifier.scopusauthoridTsao, GSW=7102813116en_HK
dc.identifier.scopusauthoridXie, D=35070710200en_HK
dc.identifier.scopusauthoridHuo, KK=7004127179en_HK
dc.identifier.scopusauthoridFu, L=22979236700en_HK
dc.identifier.scopusauthoridMa, S=16444895800en_HK
dc.identifier.scopusauthoridZheng, BJ=7201780588en_HK
dc.identifier.scopusauthoridGuan, XY=7201463221en_HK

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