The deubiquitinating enzyme USP26 is a regulator of androgen receptor signaling.
The androgen receptor (AR) is a member of the nuclear receptor superfamily and is essential for male sexual development and maturation, as well as prostate cancer development. Regulation of AR signaling activity depends on several posttranslational modifications, one of these being ubiquitination. We screened a short hairpin library targeting members of the deubiquitination enzyme family and identified the X-linked deubiquitination enzyme USP26 as a novel regulator of AR signaling. USP26 is a nuclear protein that binds to AR via three important nuclear receptor interaction motifs, and modulates AR ubiquitination, consequently influencing AR activity and stability. Our data suggest that USP26 assembles with AR and other cofactors in subnuclear foci, and serves to counteract hormone-induced AR ubiquitination, thereby contributing to the regulation of AR transcriptional activity.
Dirac
Annette M G
AM
The Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam, 1066 CX Netherlands. a.dirac@nki.nl
Bernards
René
R
D020816:Amino Acid Motifs / Q000235:genetics; D000728:Androgens / Q000378:metabolism / Q000502:physiology; D002460:Cell Line; D002467:Cell Nucleus / Q000201:enzymology / Q000235:genetics; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015723:Gene Library; D006801:Humans; D046911:Macromolecular Substances / Q000378:metabolism; D008297:Male; D011485:Protein Binding / Q000235:genetics; D011499:Protein Processing, Post-Translational / Q000235:genetics; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics*; D015533:Transcriptional Activation / Q000235:genetics; D054875:Ubiquitination / Q000235:genetics; D014452:Ubiquitins / Q000037:antagonists & inhibitors* / Q000378:metabolism*
D000728:Androgens; D046911:Macromolecular Substances; D011944:Receptors, Androgen; C501866:USP26 protein, human; D014452:Ubiquitins; D003546:Cysteine Endopeptidases