Intranuclear Translocation of Phospholipase C β2 during HL-60 Myeloid Differentiation

Abstract

Phospholipases C (PLC) β3, γ1, and γ2 were detected in nuclei of HL-60 promyelocitic leukaemia cells. When HL-60 cells undergo terminal myeloid differentiation in the presence of ATRA, the β2 isoform appeared inside nuclei and was up-regulated until 72 hours of ATRA treatment. The β3 isozyme was also increased until 72 hours and both isoforms lowered their intranuclear amount at 96 hours and following days of treatment. By contrast PLC γ1 and γ2 progressively increased in the nucleus during granulocytic differentiation even after 72 hours of treatment. Terminal differentiation was characterised by the expression of high levels of PLC γ1 and γ2 and by low levels of PLC β2 and β3 in the nucleus. PIP2and PIP hydrolysis paralleled the prevalence of the β or γ subfamily, respectively. Moreover, at all the examined times no changes of PLCs in the whole cell were detectable, indicating ade novonuclear translocation of the β2 and an increased accumulation of β3, γ1, and γ2 isoforms. Thus, the intranuclear presence, expression, and activity of PLC isozymes, which are modulated during differentiation of HL-60 cells, implicate a role for nuclear phosphoinositide signalling in the process of cell maturation. In particular the nuclear translocation of PLC β2 candidates this PLC as a key enzyme in the granulocytic differentiative commitment of HL-60 cells.