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BTG2 is an LXXLL-dependent co-repressor for androgen receptor transcriptional activity
- Source :
- Biochemical and Biophysical Research Communications. 404:903-909
- Publication Year :
- 2011
- Publisher :
- Elsevier BV, 2011.
-
Abstract
- The tumor suppressor gene, BTG2 has been down-regulated in prostate cancer and the ectopic expression of this gene has been shown to inhibit prostate cancer cell growth. Sequence analysis revealed that the BTG2 protein contains two leucine-rich motifs ((20)LxxLL(24) and (92)LxxLL(96)), which are usually found in nuclear receptor co-factors. Based on this, we postulated that there will be an association between BTG2 and AR. In this study, we discovered that BTG2 directly bound to the androgen receptor (AR) in the absence of 5α-dihydrotestosterone (DHT), and in the presence of the androgen, this interaction was increased. BTG2 bearing the mutant (20)LxxLL(24) motif bound to AR equally efficient as the wild-type BTG2, while BTG2 bearing the mutant (92)LxxLL(96) motif failed to interact with AR. Functional studies indicated that ectopic expression of BTG2 caused a significant inhibition of AR-mediated transcriptional activity and a decreased growth of prostate cancer cells. Androgen-induced promoter activation and expression of prostate-specific antigen (PSA) are significantly attenuated by BTG2. The intact (92)LxxLL(96) motif is required for these activities. These findings, for the first time, demonstrate that BTG2 complexes with AR via an LxxLL-dependent mechanism and may play a role in prostate cancer via modulating the AR signaling pathway.
- Subjects :
- Male
Transcription, Genetic
Tumor suppressor gene
Biophysics
Biology
Biochemistry
Immediate-Early Proteins
Prostate cancer
Cell Line, Tumor
medicine
Humans
Molecular Biology
Cell Proliferation
Regulation of gene expression
Leucine Zippers
BTG2
Tumor Suppressor Proteins
5-alpha-Dihydroprogesterone
Prostatic Neoplasms
Cell Biology
medicine.disease
Gene Expression Regulation, Neoplastic
Repressor Proteins
Androgen receptor
Nuclear receptor
Receptors, Androgen
Mutation
Cancer research
Ectopic expression
Signal transduction
Subjects
Details
- ISSN :
- 0006291X
- Volume :
- 404
- Database :
- OpenAIRE
- Journal :
- Biochemical and Biophysical Research Communications
- Accession number :
- edsair.doi.dedup.....00fcc0c650e205405439ea5d0d4d8c66