Abstract: 【Objective】 To investigate the influence and mechanism upon inhibition of ubiquitin-proteasome pathway on autophagy-lysosome pathway. 【Methods】 Human retinal pigment epithelial cell line ARPE-19 cells were divided into three groups according to the culture medium: DMEM group

DMEM+DMSO group

DMEM+Epoxomicin group. The expression levels of ubiquitinated proteins were analyzed by western blot and immunofluorescence to determine the UPP activity. The activity of the ALP was determined by LC3-Ⅱ

LAMP1 and LAMP2 expression

which was utilized to assess the functions of autophagy and lysosome. Meanwhile

the expression of HDAC6 and p62 were evaluated to elucidate the mechanism of the influence on ALP upon UPP inhibition. 【Results】 Inhibition of the UPP by epoxomicin resulted in aggregates of ubiquitinated proteins and protein aggregates marker γ-tubulin.The ALP was activated with the elevated level of LC3

LAMP1 and LAMP2. Levels of HDAC6 and p62 increased upon UPP inhibition

suggesting they may be involved in the activation of ALP when UPP was inhibited. 【Conclusions】 The ALP was activated and played a role in the degradation of protein aggregates as a consequence of UPP inhibition.