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dc.contributor.authorCato, L
dc.contributor.authorNeeb, A
dc.contributor.authorSharp, A
dc.contributor.authorBuzón, V
dc.contributor.authorFicarro, SB
dc.contributor.authorYang, L
dc.contributor.authorMuhle-Goll, C
dc.contributor.authorKuznik, NC
dc.contributor.authorRiisnaes, R
dc.contributor.authorNava Rodrigues, D
dc.contributor.authorArmant, O
dc.contributor.authorGourain, V
dc.contributor.authorAdelmant, G
dc.contributor.authorNtim, EA
dc.contributor.authorWesterling, T
dc.contributor.authorDolling, D
dc.contributor.authorRescigno, P
dc.contributor.authorFigueiredo, I
dc.contributor.authorFauser, F
dc.contributor.authorWu, J
dc.contributor.authorRottenberg, JT
dc.contributor.authorShatkina, L
dc.contributor.authorEster, C
dc.contributor.authorLuy, B
dc.contributor.authorPuchta, H
dc.contributor.authorTroppmair, J
dc.contributor.authorJung, N
dc.contributor.authorBräse, S
dc.contributor.authorSträhle, U
dc.contributor.authorMarto, JA
dc.contributor.authorNienhaus, GU
dc.contributor.authorAl-Lazikani, B
dc.contributor.authorSalvatella, X
dc.contributor.authorde Bono, JS
dc.contributor.authorCato, AC
dc.contributor.authorBrown, M
dc.date.accessioned2017-11-24T10:48:37Z
dc.date.issued2017-08-10
dc.identifier.citationeLife, 2017, 6
dc.identifier.issn2050-084X
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/945
dc.identifier.eissn2050-084X
dc.identifier.doi10.7554/elife.27159
dc.description.abstractTargeting the activation function-1 (AF-1) domain located in the N-terminus of the androgen receptor (AR) is an attractive therapeutic alternative to the current approaches to inhibit AR action in prostate cancer (PCa). Here we show that the AR AF-1 is bound by the cochaperone Bag-1L. Mutations in the AR interaction domain or loss of Bag-1L abrogate AR signaling and reduce PCa growth. Clinically, Bag-1L protein levels increase with progression to castration-resistant PCa (CRPC) and high levels of Bag-1L in primary PCa associate with a reduced clinical benefit from abiraterone when these tumors progress. Intriguingly, residues in Bag-1L important for its interaction with the AR AF-1 are within a potentially druggable pocket, implicating Bag-1L as a potential therapeutic target in PCa.
dc.formatElectronic
dc.languageeng
dc.language.isoeng
dc.publisherELIFE SCIENCES PUBLICATIONS LTD
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectHumans
dc.subjectProstatic Neoplasms
dc.subjectDNA-Binding Proteins
dc.subjectReceptors, Androgen
dc.subjectTranscription Factors
dc.subjectProtein Binding
dc.subjectMale
dc.subjectAndrogen Receptor Antagonists
dc.subjectProtein Interaction Maps
dc.titleDevelopment of Bag-1L as a therapeutic target in androgen receptor-dependent prostate cancer.
dc.typeJournal Article
dcterms.dateAccepted2017-08-07
rioxxterms.versionofrecord10.7554/elife.27159
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2017-08-10
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfeLife
pubs.notesNo embargo
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Computational Biology and Chemogenomics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Prostate Cancer Targeted Therapy Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Translational Therapeutics
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Computational Biology and Chemogenomics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Prostate Cancer Targeted Therapy Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Translational Therapeutics
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.publication-statusPublished
pubs.volume6
pubs.embargo.termsNo embargo
icr.researchteamComputational Biology and Chemogenomics
icr.researchteamProstate Cancer Targeted Therapy Group
icr.researchteamTranslational Therapeutics
dc.contributor.icrauthorSharp, Adam
dc.contributor.icrauthorNava Rodrigues, Daniel
dc.contributor.icrauthorRescigno, Pasquale
dc.contributor.icrauthorAl-Lazikani, Bissan
dc.contributor.icrauthorDe Bono, Johann


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