Ubiquitous Expression and Cell Cycle Regulation of the Protein Kinase PIM-1

The murinepim-1gene, isolated as a locus frequently activated by proviral integration in T cell lymphomas, encodes a protein serine kinase. Although genetic evidence suggests a crucial role for this protooncogene in cell growth and transformation, very little is known about its protein product. The murinepim-1mRNA provides alternate translational starts at a CUG codon +87–89 and an AUG codon at +339–341, in the same open reading frame (ORF), resulting in 44-kDa (397 amino acids) and 34-kDa (313 amino acids) isoforms. In this report, we demonstrate that the humanPIM-1mRNA is translated only from the single initiation methionine codon at +339–341 under cell-free conditions. Immunoblotting analyses of several human solid tumor cell lines, with highly specific antisera reveal two ubiquitously expressed isoforms (35 and 34 kDa). The estimated half-life of these proteins is shorter in the normal peripheral blood leukocytes (<5 min) than in the chronic myelogenous leukemia cells K562 (<20 min). Immunoblotting analyses of centrifugally elutriated fractions of the chronic myelogenous leukemia BV173 cells demonstrate that the levels of PIM-1 increase during the progression from early to late G1, remain high at the G1/S boundary and G2 phases of the cell cycle. The results presented here suggest a ubiquitous role for PIM-1 in progression through cell cycle.