Ubiquitous expression and cell cycle regulation of the protein kinase PIM-1.
The murine pim-1 gene, 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 murine pim-1 mRNA 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 human PIM-1 mRNA 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 GI, 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.
Liang
H
H
Department of Hematology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Hittelman
W
W
Nagarajan
L
L
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology; D003062:Codon / Q000235:genetics; D016384:Consensus Sequence; D015971:Gene Expression Regulation, Enzymologic; D006207:Half-Life; D006801:Humans; D015151:Immunoblotting; D051379:Mice; D008969:Molecular Sequence Data; D008970:Molecular Weight; D014176:Protein Biosynthesis; D017346:Protein Serine-Threonine Kinases / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D051573:Proto-Oncogene Proteins c-pim-1; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured
D003062:Codon; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; C496634:PIM1 protein, human; C496636:Pim1 protein, mouse; D017346:Protein Serine-Threonine Kinases; D051573:Proto-Oncogene Proteins c-pim-1