TSG101 interacts with the androgen receptor and attenuates its expression through the endosome/lysosome pathway
- Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan (China)
- Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Taoyuan (China)
Highlights: • TSG101interacts with AR and recruits AR to its associated late endosome structure. • TSG101 overexpression reduces AR protein level and its transactivation activity. • The downregulation of AR is mediated by TSG101 through lysosomal degradation. 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.
- OSTI ID:
- 23105719
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 503, Issue 1; Other Information: Copyright (c) 2018 Elsevier Inc. All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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