Fig. 9
From: SUMO3 modification by PIAS1 modulates androgen receptor cellular distribution and stability
Model for the regulation of AR subcellular localization and turnover by sumoylation and ubiquitination systems. In castration-resistant prostate cancer cells, the binding of androgen contained in the serum makes AR to be released from the cytoplasmic associated heat shock proteins (HSP) and translocate to the nucleus; likewise, the overexpressed PIAS1 and SUMO3 are also gathered in nucleus. SUMO3 can be conjugated to the 117th lysine of PIAS1 which is a SUMO E3 ligase itself (a), and then the sumoylated PIAS1 recruit the MDM2 protein(b) and also interact with AR through its 386th and 845th lysines, which may block the AR dimer formation (c), further resulting in the nuclear export of AR and its binding partners. The MDM2 cooperating with ubiquitin E1 and E2 promotes the polyubiquitination of AR and its subsequent proteasome-mediated degradation. The SUMO3 modification of partial AR is also accompanied in this process (d)