Investigation into the Role of Protein Phosphatase 4 Regulatory Subunits in Leukaemia
Session type: Proffered paper sessions
The serine/ threonine protein phosphatase 4 holoenzyme consists of PP4 catalytic subunit (PP4c) which interacts with four different regulatory subunits (PP4R1, PP4R2, PP4R3, PP4R4) . Our previous studies showed that PP4c has an important tumour suppressor function and plays an important role in the control of cell death and survival of both leukemic T-cells and untransformed human peripheral blood T-cells. The present work examines the effects of modulation of PP4 regulatory subunits expression on apoptosis and cell proliferation in human leukemic T-cell line Jurkat.
The human leukemic T-cell line Jurkat was transfected with siRNAs to different PP4 regulatory subunits sequences and controls received scrambled siRNA. Endogenous expression level of PP4c and PP4 regulatory subunits was confirmed by western blotting. Culture growth, cell viability, apoptosis, long term survival and cell cycle were assessed.
Down-regulation of each of the PP4 regulatory subunits greatly affected the survival and proliferation rate of Jurkat cells. Two of the regulatory subunits have pro-apoptotic function and the other two possess an anti-apoptotic role and promoted cell survival. Down-regulation of PP4 regulatory subunits had no effects on PP4c expression levels.
PP4 regulatory subunits regulate the cell survival and cell proliferation in Jurkat leukemic T-cells and exert opposing effects on cell fate. The opposing effects of the individual regulatory subunits on cell fate suggest that these subunits may function independently from PP4c. Interestingly; such opposing effects are reminiscent of other families of apoptosis-regulating genes, including the Bcl-2 gene family which encode anti- and proapoptotic members of the Bcl-2-family. The results suggest that together with PP4c, PP4 regulatory subunits constitute a family of cell fate-regulating proteins and their dysfunction may be important in the development and progression of leukaemia.