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Gene Review

Pim1  -  proviral integration site 1

Mus musculus

Synonyms: Pim-1, Serine/threonine-protein kinase pim-1
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Disease relevance of Pim1

  • Pim1 cooperates with E2a-Pbx1 to facilitate the progression of thymic lymphomas in transgenic mice [1].
  • We found retroviral integrations in c-myc and Pim1 as already reported but we also identified for the first time Notch1 as a RadLV common integration site [2].
  • Pim-1 is an oncogene activated in mouse T-cell lymphomas induced by Moloney and AKR mink cell focus (MCF) viruses [3].
  • To identify the mechanism by which the Pim kinases may affect the growth of prostate tumors, we expressed Pim-1, Pim-2, or a kinase-dead Pim-2 protein in human PC3 prostate cancer cells [4].
  • Similar to MoMuLV wild-type tumors, 50% of CD4(+)8(+) Rag-deficient tumors carry a provirus near the Pim1 protooncogene [5].

Psychiatry related information on Pim1


High impact information on Pim1


Chemical compound and disease context of Pim1


Biological context of Pim1

  • Overexpression of Pim1 can also overcome some of the proliferative defects caused by defective interleukin signaling supporting a role of Pim1 in cell proliferation [13].
  • However, Pim1 DNA rearrangements were frequently sub-stoichiometric and not present at all sites of involvement in an otherwise monoclonal lymphoma indicating that Pim1 activation occurred late in the course of lymphomagenesis [1].
  • The Pim-1 proto-oncogene is one of the most potent collaborators of the myc proto-oncogenes in inducing lymphomagenesis in mice [14].
  • Primary hematopoietic cells from Pim-2- and Pim-1/Pim-2-deficient animals failed to accumulate and underwent apoptosis in the presence of rapamycin [15].
  • The putative oncogene Pim-1 in the mouse: its linkage and variation among t haplotypes [16].

Anatomical context of Pim1


Associations of Pim1 with chemical compounds

  • The protein encoded by the qpim cDNA can autophosphorylate itself and share substrates with murine Pim-1, suggesting functional redundancy to other Pim family serine/threonine kinases [19].
  • On implantation of the transfectants in nude mice, the growth of the cells expressing Pim-1 or Pim-2 was significantly faster than the growth of the control cells transfected with the neomycin-resistant gene or the kinase-dead Pim-2 protein [4].
  • The serine/threonine kinase Pim-1 [18].
  • The association of PAP-1 with Pim-1 was also shown in vivo in transfected cells [20].
  • Pim-1 expression in situ was consistent with the documented profile of progesterone activity in mouse mammary glands [21].

Physical interactions of Pim1


Enzymatic interactions of Pim1

  • However, the Pim-1 kinase does not directly phosphorylate or bind to STAT5 [23].

Regulatory relationships of Pim1

  • The Pim1 gene was targeted by retroviral insertions in 48% of accelerated lymphomas whereas less than 5% contained activated c-Myc and none contained activated Pim2 [1].
  • Expression of a Pim-1 transgene accelerates lymphoproliferation and inhibits apoptosis in lpr/lpr mice [6].
  • Analysis of the CD25(+)/CD44(-,lo) DN subpopulation from these animals revealed that Gfi-1 inhibits and Pim-1 promotes the development of larger beta-selected cycling cells ('L subset') from smaller resting cells ('E subset') within this subpopulation [24].
  • In addition and in contrast to signaling in Mo7e and BM6 cell lines, in FDC2-ER cells SCF and Epo each were shown to rapidly activate Pim 1 gene expression [25].
  • We then investigated the signaling pathways by which CD40 regulates Pim-1 expression and found that CD40 up-regulates Pim-1 primarily via the activation of NF-kappaB [26].

Other interactions of Pim1

  • Proviral tagging in E mu-myc transgenic mice lacking the Pim-1 proto-oncogene leads to compensatory activation of Pim-2 [14].
  • We have applied proviral tagging in compound mutant Emu-myc/Pim1-/-/Pim2-/- mice to identify genes that can complement for the loss of Pim1 and Pim2 and, therefore, are able to synergize with c-myc in lymphomagenesis [13].
  • The inapt transcriptional regulation ability of the mutated Stat5b is proved by decreased levels of RNA of Stat5b-regulated genes (IL-2Rbeta and Pim1) [27].
  • The deduced amino acid (aa) sequence of the cDNA, named qpim, is more closely related to Xenopus Pim and to the recently identified rat Pim-3 than to human or rodent Pim-1 or Pim-2 [19].
  • Mapping of the Pim-1 oncogene in mouse t-haplotypes and its use to define the relative map positions of the tcl loci t0(t6) and tw12 and the marker tf (tufted) [3].

Analytical, diagnostic and therapeutic context of Pim1


  1. Pim1 cooperates with E2a-Pbx1 to facilitate the progression of thymic lymphomas in transgenic mice. Feldman, B.J., Reid, T.R., Cleary, M.L. Oncogene (1997) [Pubmed]
  2. Radiation leukemia virus common integration at the Kis2 locus: simultaneous overexpression of a novel noncoding RNA and of the proximal Phf6 gene. Landais, S., Quantin, R., Rassart, E. J. Virol. (2005) [Pubmed]
  3. Mapping of the Pim-1 oncogene in mouse t-haplotypes and its use to define the relative map positions of the tcl loci t0(t6) and tw12 and the marker tf (tufted). Ark, B., Gummere, G., Bennett, D., Artzt, K. Genomics (1991) [Pubmed]
  4. Pim family kinases enhance tumor growth of prostate cancer cells. Chen, W.W., Chan, D.C., Donald, C., Lilly, M.B., Kraft, A.S. Mol. Cancer Res. (2005) [Pubmed]
  5. PIM1 reconstitutes thymus cellularity in interleukin 7- and common gamma chain-mutant mice and permits thymocyte maturation in Rag- but not CD3gamma-deficient mice. Jacobs, H., Krimpenfort, P., Haks, M., Allen, J., Blom, B., Démollière, C., Kruisbeek, A., Spits, H., Berns, A. J. Exp. Med. (1999) [Pubmed]
  6. Expression of a Pim-1 transgene accelerates lymphoproliferation and inhibits apoptosis in lpr/lpr mice. Möröy, T., Grzeschiczek, A., Petzold, S., Hartmann, K.U. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  7. Murine leukemia virus-induced T-cell lymphomagenesis: integration of proviruses in a distinct chromosomal region. Cuypers, H.T., Selten, G., Quint, W., Zijlstra, M., Maandag, E.R., Boelens, W., van Wezenbeek, P., Melief, C., Berns, A. Cell (1984) [Pubmed]
  8. Synergistic roles for Pim-1 and c-Myc in STAT3-mediated cell cycle progression and antiapoptosis. Shirogane, T., Fukada, T., Muller, J.M., Shima, D.T., Hibi, M., Hirano, T. Immunity (1999) [Pubmed]
  9. Pim-1 kinase and p100 cooperate to enhance c-Myb activity. Leverson, J.D., Koskinen, P.J., Orrico, F.C., Rainio, E.M., Jalkanen, K.J., Dash, A.B., Eisenman, R.N., Ness, S.A. Mol. Cell (1998) [Pubmed]
  10. Impaired interleukin-3 response in Pim-1-deficient bone marrow-derived mast cells. Domen, J., van der Lugt, N.M., Laird, P.W., Saris, C.J., Clarke, A.R., Hooper, M.L., Berns, A. Blood (1993) [Pubmed]
  11. Pim-1 protein kinase is nuclear in Burkitt's lymphoma: nuclear localization is necessary for its biologic effects. Ionov, Y., Le, X., Tunquist, B.J., Sweetenham, J., Sachs, T., Ryder, J., Johnson, T., Lilly, M.B., Kraft, A.S. Anticancer Res. (2003) [Pubmed]
  12. Pim-1 kinase stability is regulated by heat shock proteins and the ubiquitin-proteasome pathway. Shay, K.P., Wang, Z., Xing, P.X., McKenzie, I.F., Magnuson, N.S. Mol. Cancer Res. (2005) [Pubmed]
  13. Identification and characterization of collaborating oncogenes in compound mutant mice. Berns, A., Mikkers, H., Krimpenfort, P., Allen, J., Scheijen, B., Jonkers, J. Cancer Res. (1999) [Pubmed]
  14. Proviral tagging in E mu-myc transgenic mice lacking the Pim-1 proto-oncogene leads to compensatory activation of Pim-2. van der Lugt, N.M., Domen, J., Verhoeven, E., Linders, K., van der Gulden, H., Allen, J., Berns, A. EMBO J. (1995) [Pubmed]
  15. Pim and Akt oncogenes are independent regulators of hematopoietic cell growth and survival. Hammerman, P.S., Fox, C.J., Birnbaum, M.J., Thompson, C.B. Blood (2005) [Pubmed]
  16. The putative oncogene Pim-1 in the mouse: its linkage and variation among t haplotypes. Nadeau, J.H., Phillips, S.J. Genetics (1987) [Pubmed]
  17. The Pim kinases control rapamycin-resistant T cell survival and activation. Fox, C.J., Hammerman, P.S., Thompson, C.B. J. Exp. Med. (2005) [Pubmed]
  18. The serine/threonine kinase Pim-1. Bachmann, M., Möröy, T. Int. J. Biochem. Cell Biol. (2005) [Pubmed]
  19. Developmental expression of pim kinases suggests functions also outside of the hematopoietic system. Eichmann, A., Yuan, L., Bréant, C., Alitalo, K., Koskinen, P.J. Oncogene (2000) [Pubmed]
  20. PAP-1, a novel target protein of phosphorylation by pim-1 kinase. Maita, H., Harada, Y., Nagakubo, D., Kitaura, H., Ikeda, M., Tamai, K., Takahashi, K., Ariga, H., Iguchi-Ariga, S.M. Eur. J. Biochem. (2000) [Pubmed]
  21. Pim-1 kinase expression during murine mammary development. Gapter, L.A., Magnuson, N.S., Ng, K.Y., Hosick, H.L. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  22. Pim-1 kinase phosphorylates RUNX family transcription factors and enhances their activity. Aho, T.L., Sandholm, J., Peltola, K.J., Ito, Y., Koskinen, P.J. BMC Cell Biol. (2006) [Pubmed]
  23. Pim-1 kinase inhibits STAT5-dependent transcription via its interactions with SOCS1 and SOCS3. Peltola, K.J., Paukku, K., Aho, T.L., Ruuska, M., Silvennoinen, O., Koskinen, P.J. Blood (2004) [Pubmed]
  24. Evidence implicating Gfi-1 and Pim-1 in pre-T-cell differentiation steps associated with beta-selection. Schmidt, T., Karsunky, H., Rödel, B., Zevnik, B., Elsässer, H.P., Möröy, T. EMBO J. (1998) [Pubmed]
  25. Mechanisms of stem cell factor and erythropoietin proliferative co-signaling in FDC2-ER cells. Joneja, B., Chen, H.C., Seshasayee, D., Wrentmore, A.L., Wojchowski, D.M. Blood (1997) [Pubmed]
  26. CD40 signaling in B cells regulates the expression of the Pim-1 kinase via the NF-kappa B pathway. Zhu, N., Ramirez, L.M., Lee, R.L., Magnuson, N.S., Bishop, G.A., Gold, M.R. J. Immunol. (2002) [Pubmed]
  27. A mutant Stat5b with weaker DNA binding affinity defines a key defective pathway in nonobese diabetic mice. Davoodi-Semiromi, A., Laloraya, M., Kumar, G.P., Purohit, S., Jha, R.K., She, J.X. J. Biol. Chem. (2004) [Pubmed]
  28. Sequence tags of provirus integration sites in DNAs of tumors induced by the murine retrovirus SL3-3. Sørensen, A.B., Duch, M., Amtoft, H.W., Jørgensen, P., Pedersen, F.S. J. Virol. (1996) [Pubmed]
  29. Pim-1 associates with protein complexes necessary for mitosis. Bhattacharya, N., Wang, Z., Davitt, C., McKenzie, I.F., Xing, P.X., Magnuson, N.S. Chromosoma (2002) [Pubmed]
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