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Conference Paper: CHD1L suppresses the nucleus-to-mitochondria translocation of Nur77 to sustain hepatocellular carcinoma cell survival

TitleCHD1L suppresses the nucleus-to-mitochondria translocation of Nur77 to sustain hepatocellular carcinoma cell survival
Authors
Issue Date2009
PublisherAmerican Association for Cancer Research
Citation
The 100th Annual Meeting of the American Association for Cancer Research, Denver, CO, 18-22 April 2009. In Cancer Research, 2009, v. 69, Abstract no. 3458 How to Cite?
AbstractChromodomain helicase/ATPase DNA binding protein 1-like gene (CHD1L), also named amplified in liver cancer 1 (ALC1), is a recently identified oncogene localized at 1q21, one of the most frequently amplified chromosomal regions in hepatocellular carcinoma (HCC). Our previous studies demonstrated that CHD1L confers high susceptibility to spontaneous hepatocarcinogenesis and HCC formation and development, lending a support to our hypothesis that CHD1L is the target oncogene responsible for the 1q21 amplification event. Recenly, by yeast-two hybrid assay, a key apoptosis mediator Nur77 was revealed to bind CHD1L. In this study, as the first cellular protein identified to bind Nur77, CHD1L are able to inhibit the nucleus-to-mitochondria translocation of Nur77, resulting in the hinderance of cytochrome c (Cyt c) release and the subsequent caspase activation and apoptosis. Further studies found that 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 there existed a reverse correlation between CHD1L expression level and the rate of apoptosis among eight HCC cell lines and two normal liver cell lines, and the nucleus-to-mitochondria translocation of Nur77 was inhibited in HepG2 cells with the high level of endogenous CHD1L expression, suggesting the inhibition of Nur77-mediated apoptosis by endogenous CHD1L is a critical biological process in hepatocarcinogenesis. Overall, the mechanistic study on CHD1L defines a novel pathway in HCC progression to enhance cell survival by preventing Nur77-mediated apoptosis, which could be suggested as the reason for CHD1L oncogenicity and used as great implications for HCC therapeutics.
Persistent Identifierhttp://hdl.handle.net/10722/62706
ISSN
2015 Impact Factor: 8.556
2015 SCImago Journal Rankings: 5.372

 

DC FieldValueLanguage
dc.contributor.authorChen, Len_HK
dc.contributor.authorHu, Len_HK
dc.contributor.authorChan, HMen_HK
dc.contributor.authorGuan, XYen_HK
dc.date.accessioned2010-07-13T04:07:25Z-
dc.date.available2010-07-13T04:07:25Z-
dc.date.issued2009en_HK
dc.identifier.citationThe 100th Annual Meeting of the American Association for Cancer Research, Denver, CO, 18-22 April 2009. In Cancer Research, 2009, v. 69, Abstract no. 3458-
dc.identifier.issn0008-5472-
dc.identifier.urihttp://hdl.handle.net/10722/62706-
dc.description.abstractChromodomain helicase/ATPase DNA binding protein 1-like gene (CHD1L), also named amplified in liver cancer 1 (ALC1), is a recently identified oncogene localized at 1q21, one of the most frequently amplified chromosomal regions in hepatocellular carcinoma (HCC). Our previous studies demonstrated that CHD1L confers high susceptibility to spontaneous hepatocarcinogenesis and HCC formation and development, lending a support to our hypothesis that CHD1L is the target oncogene responsible for the 1q21 amplification event. Recenly, by yeast-two hybrid assay, a key apoptosis mediator Nur77 was revealed to bind CHD1L. In this study, as the first cellular protein identified to bind Nur77, CHD1L are able to inhibit the nucleus-to-mitochondria translocation of Nur77, resulting in the hinderance of cytochrome c (Cyt c) release and the subsequent caspase activation and apoptosis. Further studies found that 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 there existed a reverse correlation between CHD1L expression level and the rate of apoptosis among eight HCC cell lines and two normal liver cell lines, and the nucleus-to-mitochondria translocation of Nur77 was inhibited in HepG2 cells with the high level of endogenous CHD1L expression, suggesting the inhibition of Nur77-mediated apoptosis by endogenous CHD1L is a critical biological process in hepatocarcinogenesis. Overall, the mechanistic study on CHD1L defines a novel pathway in HCC progression to enhance cell survival by preventing Nur77-mediated apoptosis, which could be suggested as the reason for CHD1L oncogenicity and used as great implications for HCC therapeutics.-
dc.languageengen_HK
dc.publisherAmerican Association for Cancer Research-
dc.relation.ispartofCancer Research-
dc.titleCHD1L suppresses the nucleus-to-mitochondria translocation of Nur77 to sustain hepatocellular carcinoma cell survivalen_HK
dc.typeConference_Paperen_HK
dc.identifier.emailChen, L: leileichen79@hotmail.comen_HK
dc.identifier.emailHu, L: lhuc@hkusua.hku.hken_HK
dc.identifier.emailChan, HM: chantimtam@msn.comen_HK
dc.identifier.emailGuan, XY: xyguan@hkucc.hku.hken_HK
dc.identifier.authorityGuan, XY=rp00454en_HK
dc.identifier.hkuros156548en_HK

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