Fig. 7

Negative regulation of the HSPA1B by UBASH3A controls cell proliferation. A, B Expression of HSPA1B in shUBASH3B (A) and shUBASH3A1 (B) cells, via RT-qPCR. C, D Expression of FLI1 (C) and HSPA1B (D) in shFLI1 cells via RT-qPCR. E lentivirus-mediated downregulation of HSPA1B in HEL cells using the shHSPA1B1-3 expression vector, as determined via RT-qPCR. F The proliferation of shHSPA1B3 and scrambled control cells for the indicated days was assessed using an MTT assay. P < 0.01 (**), P < 0.001 (***). G Model showing the effect of FLI1 on UBASH3A and UBASH3B expression as well as erythroleukemia progression. UBASH3B induction via FLI1 overexpression suppresses PKCẟ and increased cell survival as well as drug resistance. Higher UBASH3B transcription following FLI1 overexpression also causes inhibition of AP1, which would otherwise suppress leukemia progression. In addition, UBASH3B controls the expression of SYK and partially contributes to erythroleukemia progression. Suppression of UBASH3A transcription via FLI1 overexpression increases the expression of leukemia growth suppressor HSPA1B, which blocks proliferation. On the other hand, activation of UBASH3B by FLI1 further decreases HSPA1B expression, causing acceleration of cell proliferation. Dotted lines represent indirect regulation