To investigate the function of the hinge region in transcriptional activation by the androgen receptor, we compared the actions of the wild-type receptor with a mutant receptor, deleted of amino acids 628-646 of the hinge. The role of the proteasome on the expression and activity of these two proteins was investigated. The deletion mutant demonstrated a threefold increase in transcriptional activity when compared to the wild-type receptor protein. Furthermore, we found that hormone-dependent stabilization of the receptor protein was more enhanced for the deletion mutant. In addition, experiments using the proteasome inhibitor, MG132, demonstrated that the deletion mutant is more sensitive to proteasome-mediated degradation than the wild-type receptor. However, inhibition of the proteasome had a negative effect on the transcriptional activity of the deletion mutant. Taken together, our results suggest that the hinge region not only plays an important role in controlling the transactivation potential of the androgen receptor but also in determining the influence of the proteasome on androgen receptor-mediated transcriptional activation.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1196/annals.1329.068 | DOI Listing |
J Neurosci
January 2025
Flaum Eye Institute, Department of Ophthalmology, University of Rochester Medical Center, Rochester, New York, 14642, USA;
The inner ear houses both hearing and balance sensory modalities. The hearing and balance organs consist of similar cell types, including sensory hair cells and associated supporting cells. Previously we showed that is required for maintaining supporting cell survival during cochlear maturation.
View Article and Find Full Text PDFNature
January 2025
Department of Medical Oncology and Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA, USA.
Oncogenic mutations that drive colorectal cancer can be present in healthy intestines for long periods without overt consequence. Mutation of Adenomatous polyposis coli (Apc), the most common initiating event in conventional adenomas, activates Wnt signalling, hence conferring fitness on mutant intestinal stem cells (ISCs). Apc mutations may occur in ISCs that arose by routine self-renewal or by dedifferentiation of their progeny.
View Article and Find Full Text PDFPlant Mol Biol
January 2025
National Key Laboratory for Tropical Crop Breeding, Tropical Crop Genetic Resources Institute, Chinese Academy of Tropical Agricultural Sciences, Sanya, Haikou, 572024/571101, Hainan, China.
Arabidopsis MYB transcription factor, AtDUO1 regulates generative cell body (GC) morphogenesis from round to semi and fully elongated forms before pollen mitosis-II (PM II). It was hypothesised that DUO1 might regulate morphogenesis through any of its direct target genes or components of the DUO1-DAZ1 network. The developmental analysis of plants harbouring T-DNA insertions in some DUO1 target genes using light and fluorescence microscopy revealed abnormal GC morphogenesis only in daz1 and daz2, but gcs1, trm16, mapkkk10, mapkkk20, tet11, and tip1 all undergo normal elongation indicating that these target genes have no important roles in morphogenesis or may be redundant.
View Article and Find Full Text PDFPLoS One
January 2025
Department of Microbiology and Immunology, McGill University, Montreal, Quebec, Canada.
The ability to determine the essentiality of a gene in the protozoan parasite Leishmania is important to identify potential targets for intervention and understanding the parasite biology. CRISPR gene editing technology has significantly improved gene targeting efficiency in Leishmania. There are two commonly used CRISPR gene targeting methods in Leishmania; the stable expression of the gRNA and Cas9 using a plasmid containing a Leishmania ribosomal RNA gene promoter (rRNA-P stable protocol) and the T7 RNA polymerase based transient gRNA expression system in promastigotes stably expressing Cas9 (T7 transient protocol).
View Article and Find Full Text PDFViruses
November 2024
Laboratory for Microbiology, Parasitology and Hygiene, Infla-Med Centre of Excellence, University of Antwerp (UA), Universiteitsplein 1 S.7, 2610 Antwerp, Belgium.
Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infections in young children, elderly and immunocompromised patients worldwide. The RSV fusion (F) protein, which has 5-6 N-glycosylation sites depending on the strain, is a major target for vaccine development. Two to three of these sites are located in the p27 peptide, which is considered absent in virions.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!