Arsenic Trioxide Induce the Upregulation of β1-Subunit of Proteasome in NB4 Cell.

Abstract

Arsenic trioxide has proven efficacy in inducing molecular remission in patients with acute promyelocytic leukemia (APL). The degradation of PML-RARα fusion protein induced by arsenic trioxide is related to its clinical efficacy in APL. The ubiquitin (Ub)/ proteasome pathway may involved in the degradation, but the mechanism in detail is unclear. In our previous study, we found that PSMB6 gene which encoded the β1-subunit of 26s proteasome was up-regulated after the treatment of arsenic trioxide (0.5 mmol/L). In current study, by western-blot analysis, we investigated the expression of β1-subunit of 26s proteasome after As2O3 exposure. We found that β1-subunit of 26s proteasome was upregulated after 24h treatment of As2O3(0.5 mmol/L). But the expression of β1-subunit of 26s proteasome return to baseline after 48h treatment. These findings are consistent with the results of the degradation of PML-RARα fusion protein. It is well known that the differentiation and apoptosis of NB4 cells are associated with the degradation of PML-RARα fusion protein and the reconstitution of the nuclear bodys (NBs). These results indicate that increase of β1-subunit of 26s may be associated with the degradation of fusion protein and the NB reorganization and play roles in the differentiation and apoptosis of NB4 cells. This pathway employs a complex enzymatic system to degrade proteins and whether other subunits are involved in the process is still unclear.