Calcium-dependent and oncogenic IL-3 mRNA stabilization can be distinguished pharmacologically and by sequence requirements in the 3 ' UTR

In interleukin-3 (IL-3)-dependent PB-3c mast cells, the normally short-live d IL-3 mRNA is stabilized upon calcium-ionophore treatment or following v-H -ras induced oncogenesis, We compared the underlying stabilization mechanis ms by analysing the response to the posttranscriptionally acting drugs cycl osporin A (CsA), FK506 and SB202190, Stable IL-3 transcripts in the PB-3c-d erived tumour cell line V2D1 decayed in response to CsA and FK506, but not in response to SB202190. Transcripts stabilized by elevating intracellular calcium Levels in PB-3c cells were destabilized in response to all three dr ugs. In PB-3c cells, six AUUUA pentamers within the AU-rich element were su fficient to confer responsiveness to calcium-ionophore and CsA treatment. I n V2D1 tumour cells, sensitivity to CsA required additional nucleotides fla nking these pentamers, Our data suggest that IL-3 mRNA stabilization by eit her calcium-dependent or oncogenic pathways involves different intracellula r mechanisms.