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Article: Anthracyclines disrupt telomere maintenance by telomerase through inducing PinX1 ubiquitination and degradation

TitleAnthracyclines disrupt telomere maintenance by telomerase through inducing PinX1 ubiquitination and degradation
Authors
Issue Date2012
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/onc
Citation
Oncogene, 2012, v. 31 n. 1, p. 1-12 How to Cite?
Abstract
Telomere maintenance is essential for cancer growth. Induction of telomere dysfunction, for example, by inhibition of telomeric proteins or telomerase, has been shown to strongly enhance cancer cells sensitivity to chemotherapies. However, it is not clear whether modulations of telomere maintenance constitute cancer cellular responses to chemotherapies. Furthermore, the manner in which anti-cancer drugs affect telomere function remains unknown. In this study, we show that anthracyclines, a class of anti-cancer drugs widely used in clinical cancer treatments, have an active role in triggering telomere dysfunction specifically in telomerase-positive cancer cells. Anthracyclines interrupt telomere maintenance by telomerase through the downregulation of PinX1, a protein factor responsible for targeting telomerase onto telomeres, thereby inhibiting telomerase association with telomeres. We further demonstrate that anthracyclines downregulate PinX1 by inducing this protein degradation through the ubiquitin-proteasome-dependent pathway. Our data not only reveal a novel action for anthracyclines as telomerase functional inhibitors but also provide a clue for the development of novel anti-cancer drugs based on telomerase/telomere targeting, which is actively investigated by many current studies. © 2012 Macmillan Publishers Limited All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/168600
ISSN
2013 Impact Factor: 8.559
2013 SCImago Journal Rankings: 4.764
ISI Accession Number ID
References

 

Author Affiliations
  1. Guangdong Provincial People's Hospital
  2. Sun Yat-Sen University
  3. Beijing Institute of Biotechnology
  4. Chinese University of Hong Kong
DC FieldValueLanguage
dc.contributor.authorZhang, Ben_US
dc.contributor.authorQian, Den_US
dc.contributor.authorMa, HHen_US
dc.contributor.authorJin, Ren_US
dc.contributor.authorYang, PXen_US
dc.contributor.authorCai, MYen_US
dc.contributor.authorLiu, YHen_US
dc.contributor.authorLiao, YJen_US
dc.contributor.authorDeng, HXen_US
dc.contributor.authorMai, SJen_US
dc.contributor.authorZhang, Hen_US
dc.contributor.authorZeng, YXen_US
dc.contributor.authorLin, MCen_US
dc.contributor.authorKung, HFen_US
dc.contributor.authorXie, Den_US
dc.contributor.authorHuang, JJen_US
dc.date.accessioned2012-10-08T03:21:23Z-
dc.date.available2012-10-08T03:21:23Z-
dc.date.issued2012en_US
dc.identifier.citationOncogene, 2012, v. 31 n. 1, p. 1-12en_US
dc.identifier.issn0950-9232en_US
dc.identifier.urihttp://hdl.handle.net/10722/168600-
dc.description.abstractTelomere maintenance is essential for cancer growth. Induction of telomere dysfunction, for example, by inhibition of telomeric proteins or telomerase, has been shown to strongly enhance cancer cells sensitivity to chemotherapies. However, it is not clear whether modulations of telomere maintenance constitute cancer cellular responses to chemotherapies. Furthermore, the manner in which anti-cancer drugs affect telomere function remains unknown. In this study, we show that anthracyclines, a class of anti-cancer drugs widely used in clinical cancer treatments, have an active role in triggering telomere dysfunction specifically in telomerase-positive cancer cells. Anthracyclines interrupt telomere maintenance by telomerase through the downregulation of PinX1, a protein factor responsible for targeting telomerase onto telomeres, thereby inhibiting telomerase association with telomeres. We further demonstrate that anthracyclines downregulate PinX1 by inducing this protein degradation through the ubiquitin-proteasome-dependent pathway. Our data not only reveal a novel action for anthracyclines as telomerase functional inhibitors but also provide a clue for the development of novel anti-cancer drugs based on telomerase/telomere targeting, which is actively investigated by many current studies. © 2012 Macmillan Publishers Limited All rights reserved.en_US
dc.languageengen_US
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/oncen_US
dc.relation.ispartofOncogeneen_US
dc.subject.meshAnthracyclines - Pharmacologyen_US
dc.subject.meshCell Line, Tumoren_US
dc.subject.meshDna Damageen_US
dc.subject.meshHumansen_US
dc.subject.meshProteasome Endopeptidase Complex - Physiologyen_US
dc.subject.meshTelomerase - Physiologyen_US
dc.subject.meshTelomere - Drug Effectsen_US
dc.subject.meshTumor Suppressor Proteins - Metabolismen_US
dc.subject.meshUbiquitinationen_US
dc.titleAnthracyclines disrupt telomere maintenance by telomerase through inducing PinX1 ubiquitination and degradationen_US
dc.typeArticleen_US
dc.identifier.emailLin, MC:mcllin@hkucc.hku.hken_US
dc.identifier.authorityLin, MC=rp00746en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1038/onc.2011.214en_US
dc.identifier.pmid21643006en_US
dc.identifier.scopuseid_2-s2.0-84855343604en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-84855343604&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume31en_US
dc.identifier.issue1en_US
dc.identifier.spage1en_US
dc.identifier.epage12en_US
dc.identifier.isiWOS:000299176200001-
dc.publisher.placeUnited Kingdomen_US
dc.identifier.scopusauthoridZhang, B=35222603300en_US
dc.identifier.scopusauthoridQian, D=54584201800en_US
dc.identifier.scopusauthoridMa, HH=54882246700en_US
dc.identifier.scopusauthoridJin, R=54882249200en_US
dc.identifier.scopusauthoridYang, PX=15764055700en_US
dc.identifier.scopusauthoridCai, MY=23388510500en_US
dc.identifier.scopusauthoridLiu, YH=36014503900en_US
dc.identifier.scopusauthoridLiao, YJ=36114448500en_US
dc.identifier.scopusauthoridDeng, HX=24079601100en_US
dc.identifier.scopusauthoridMai, SJ=36780688900en_US
dc.identifier.scopusauthoridZhang, H=40662127200en_US
dc.identifier.scopusauthoridZeng, YX=39863826600en_US
dc.identifier.scopusauthoridLin, MC=7404816359en_US
dc.identifier.scopusauthoridKung, HF=7402514190en_US
dc.identifier.scopusauthoridXie, D=35070710200en_US
dc.identifier.scopusauthoridHuang, JJ=7407194640en_US
dc.identifier.citeulike9432262-

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