TSG101 interacts with the androgen receptor and attenuates its expression through the endosome/lysosome pathway.

The androgen receptor (AR) signaling pathway plays a vital role in the normal development and function of the male reproductive organs. Dysregulation of the androgen-AR signaling pathway has been linked to prostate cancer. Here, we demonstrate that tumor susceptibility gene 101 (TSG101) regulates AR expression level via the endosome/lysosome degradation ...
pathway. In LNCaP cells, TSG101 overexpression recruits the AR to TSG101-containing cytoplasmic vesicles resulting in reduced AR protein level and AR transactivation activity downregulation. Immunofluorescence microscopy demonstrated that TSG101-decorated cytoplasmic vesicles are associated with late endosomes/lysosomes and the AR could be found within the Lamp2 positive TSG101 vesicles upon lysosomal protease inhibitor treatment. Furthermore, chloroquine or bafilomycin A1 treatment was able to restore TSG101-mediated AR expression reduction. Based on these data, we conclude that the interaction of the AR and TSG101 leads to AR recruitment to TSG101-containing cytoplasmic vesicles and induces AR-attenuated expression through the late endosome/lysosome degradation pathway.
Mesh Terms:
Cell Line, Tumor, DNA-Binding Proteins, Down-Regulation, Endosomal Sorting Complexes Required for Transport, Endosomes, Gene Expression Regulation, Neoplastic, HEK293 Cells, Humans, Lysosomal-Associated Membrane Protein 2, Lysosomes, Male, Prostatic Neoplasms, Receptors, Androgen, Signal Transduction, Transcription Factors, Transcriptional Activation
Biochem. Biophys. Res. Commun.
Date: Dec. 03, 2017
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