RRC ID 60015
Author Liu Y, Wang Y, Wang F, Pan J, Xu J, Li J, Zhou C, Ding G, Wu Y, Liu X, Sheng J, Huang H.
Title Mechanism underlying the retarded nuclear translocation of androgen receptor splice variants.
Journal Sci China Life Sci
Abstract As shown in our previous study, two alternatively spliced androgen receptor (AR) variants, which are exclusively expressed in the granulosa cells of patients with polycystic ovary syndrome, exhibit retarded nuclear translocation compared with wild-type AR. However, researchers have not yet determined whether these abnormalities correlate with heat shock protein 90 (HSP90) and importin α (the former is a generally accepted co-chaperone of AR, and the latter is a component of classical nuclear import complexes). Here, these two variants were mainly retained in cytoplasm with HSP90 and importin α in the presence of dihydrotestosterone (DHT), and their levels in nucleus were significantly reduced, according to the immunofluorescence staining. The binding affinity of two AR variants for importin α was consistently decreased, while it was increased in WT-AR following DHT stimulation, leading to reduced nuclear import, particularly for the insertion-AR (Ins-AR). However, the binding affinities of two AR variants for HSP90 were increased in the absence of DHT compared with WT-AR, which functioned to maintain spatial structural stability, particularly for the deletion-AR (Del-AR). Therefore, the retarded nuclear translocation of two AR variants is associated with HSP90 and importin α, and the abnormal binding affinities for them play critical roles in this process.
Volume 62(2)
Pages 257-267
Published 2019-2-1
DOI 10.1007/s11427-018-9379-x
PII 10.1007/s11427-018-9379-x
PMID 30267260
MeSH Active Transport, Cell Nucleus Alternative Splicing Cell Line, Tumor Cell Nucleus / metabolism* Cytoplasm / metabolism Dihydrotestosterone / pharmacology Female Gene Expression HEK293 Cells HSP90 Heat-Shock Proteins / metabolism* Humans Polycystic Ovary Syndrome / metabolism Protein Binding / drug effects Receptors, Androgen / genetics* Receptors, Androgen / metabolism* alpha Karyopherins / metabolism*
IF 3.583
Times Cited 2
Human and Animal Cells KGN(RCB1154) 293T(RCB2202)