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Article: Anthracyclines disrupt telomere maintenance by telomerase through inducing PinX1 ubiquitination and degradation
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TitleAnthracyclines disrupt telomere maintenance by telomerase through inducing PinX1 ubiquitination and degradation
 
AuthorsZhang, B2
Qian, D2
Ma, HH3
Jin, R3
Yang, PX3
Cai, MY2
Liu, YH1
Liao, YJ2
Deng, HX2
Mai, SJ2
Zhang, H3
Zeng, YX2
Lin, MC4
Kung, HF2 4
Xie, D2
Huang, JJ3
 
Issue Date2012
 
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/onc
 
CitationOncogene, 2012, v. 31 n. 1, p. 1-12 [How to Cite?]
DOI: http://dx.doi.org/10.1038/onc.2011.214
 
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.
 
ISSN0950-9232
2013 Impact Factor: 8.559
2013 SCImago Journal Rankings: 4.764
 
DOIhttp://dx.doi.org/10.1038/onc.2011.214
 
ISI Accession Number IDWOS:000299176200001
 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorZhang, B
 
dc.contributor.authorQian, D
 
dc.contributor.authorMa, HH
 
dc.contributor.authorJin, R
 
dc.contributor.authorYang, PX
 
dc.contributor.authorCai, MY
 
dc.contributor.authorLiu, YH
 
dc.contributor.authorLiao, YJ
 
dc.contributor.authorDeng, HX
 
dc.contributor.authorMai, SJ
 
dc.contributor.authorZhang, H
 
dc.contributor.authorZeng, YX
 
dc.contributor.authorLin, MC
 
dc.contributor.authorKung, HF
 
dc.contributor.authorXie, D
 
dc.contributor.authorHuang, JJ
 
dc.date.accessioned2012-10-08T03:21:23Z
 
dc.date.available2012-10-08T03:21:23Z
 
dc.date.issued2012
 
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.
 
dc.description.naturelink_to_subscribed_fulltext
 
dc.identifier.citationOncogene, 2012, v. 31 n. 1, p. 1-12 [How to Cite?]
DOI: http://dx.doi.org/10.1038/onc.2011.214
 
dc.identifier.citeulike9432262
 
dc.identifier.doihttp://dx.doi.org/10.1038/onc.2011.214
 
dc.identifier.epage12
 
dc.identifier.isiWOS:000299176200001
 
dc.identifier.issn0950-9232
2013 Impact Factor: 8.559
2013 SCImago Journal Rankings: 4.764
 
dc.identifier.issue1
 
dc.identifier.pmid21643006
 
dc.identifier.scopuseid_2-s2.0-84855343604
 
dc.identifier.spage1
 
dc.identifier.urihttp://hdl.handle.net/10722/168600
 
dc.identifier.volume31
 
dc.languageeng
 
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/onc
 
dc.publisher.placeUnited Kingdom
 
dc.relation.ispartofOncogene
 
dc.relation.referencesReferences in Scopus
 
dc.subject.meshAnthracyclines - Pharmacology
 
dc.subject.meshCell Line, Tumor
 
dc.subject.meshDna Damage
 
dc.subject.meshHumans
 
dc.subject.meshProteasome Endopeptidase Complex - Physiology
 
dc.subject.meshTelomerase - Physiology
 
dc.subject.meshTelomere - Drug Effects
 
dc.subject.meshTumor Suppressor Proteins - Metabolism
 
dc.subject.meshUbiquitination
 
dc.titleAnthracyclines disrupt telomere maintenance by telomerase through inducing PinX1 ubiquitination and degradation
 
dc.typeArticle
 
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<description.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. &#169; 2012 Macmillan Publishers Limited All rights reserved.</description.abstract>
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Author Affiliations
  1. Guangdong Provincial People's Hospital
  2. Sun Yat-Sen University
  3. Beijing Institute of Biotechnology
  4. Chinese University of Hong Kong