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| Status |
Public on Aug 23, 2017 |
| Title |
Targeting the androgen receptor N-terminus via the cochaperone Bag-1L [ChIP-Seq] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Targeting the activation function-1 (AF-1) at 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 BAG domain of the cochaperone Bag-1L. Mutations in this domain or loss of Bag-1L abrogates AR signaling and reduces PCa growth. Correspondingly, Bag-1L protein levels increase with progression of primary prostate tumors to castration-resistant PCa, correlating inversely with patient response to abiraterone therapy. Intriguingly, BAG domain residues important for its interaction with the AR AF-1 overlap a potentially druggable pocket of this protein. Bag-1L is therefore a putative therapeutic target for the inhibition of AR AF-1 activity.
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| Overall design |
Androgen receptor (AR) ChIP-seq was carried out in LNCaP Talen Control, Bag-1L KO, Bag-1L KO plus Vector (control), Bag-1L KO plus (wild-type) Bag-1L, LNCaP plus wild-type Bag-1L and LNCaP plus CMut Bag-1L cells. Cells were cultured under hormone-starvation conditions for 72 h and then treated with vehicle (ETOH) or 10 nM DHT for 4 h prior to cell fixation and harvest. Experiments in LnCaP Talen Control and Bag-1L KO cells were carried out in duplicate.
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| Contributor(s) |
Cato L, Wu J, Cato AC, Brown M |
| Citation(s) |
28826504, 35479411 |
| |
| Submission date |
Nov 16, 2016 |
| Last update date |
May 05, 2022 |
| Contact name |
Laura Cato |
| E-mail(s) |
laura_cato@dfci.harvard.edu
|
| Organization name |
Dana-Farber Cancer Institute
|
| Department |
Medical Oncology
|
| Street address |
450 Brookline Ave., D728
|
| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02215 |
| Country |
USA |
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| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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| Samples (24)
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| This SubSeries is part of SuperSeries: |
| GSE89939 |
Targeting the androgen receptor N-terminus via the cochaperone Bag-1L |
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| Relations |
| BioProject |
PRJNA354526 |
| SRA |
SRP096060 |
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