[Effects of Ubiquitination on the Expression of BCL6 Protein，Cell Proliferation and Apoptosis in K562/G01 Cells].

Objective: To explore the the effects of ubiquitin-proteasome system (UPS) on BCL6 protein level，proliferation and apoptosis of cell imatinib（IM）-resistant K562/G01 cells.
Methods: Western blot was used to detect the expression of BCL6 in K562/G01 cells before and after treatment with protease inhibitor MG-132.The RT-PCR and Western blot respectively were used to detect the mRNA and protein expression levels of BCL6 and USP2 in K562/G01 cells treated with or without ML364 (a ubiquitin-specific protease USP2 inhibitor). The effects of IM alone or in combination with ML364 on proliferation and apoptosis of K562/G01 were analysed by CCK-8 method and flow cytometry.
Results: After treatment with protease inhibitor MG132, the BCL6 protein level of K562/G01 significantly increased (P<0.05). The mRNA and protein expression level of ubiquitin-specific protease USP2 in K562/G01 cell line was higher than that in K562 cell line (P<0.05). After treatment of K562/G01 with USP2 protease inhibitor ML364, the expression levels of USP2 and BCL6 proteins were down-regulated simultaneously (P<0.05) . After combination of ML364 and IM, both the proliferation inhibitory rate and the apoptosis rate of K562/G01 cells significantly increased(P<0.05).
Conclusion: ML364 decreases the BCL6 protein stability in K562/G01 by inhibiting the USP2-mediated deubiquitination, and down-regulate the BCL6 protein experssion, thereby increases the sensitivity of drug-resistant cells to IM.