Available structures
PDBOrtholog search: PDBe RCSB
AliasesPIM1, PIM, Pim-1 proto-oncogene, serine/threonine kinase
External IDsOMIM: 164960 MGI: 97584 HomoloGene: 11214 GeneCards: PIM1
RefSeq (mRNA)



RefSeq (protein)



Location (UCSC)Chr 6: 37.17 – 37.18 MbChr 17: 29.71 – 29.72 Mb
PubMed search[3][4]
View/Edit HumanView/Edit Mouse

Proto-oncogene serine/threonine-protein kinase Pim-1 is an enzyme that in humans is encoded by the PIM1 gene.[5][6][7]

Pim-1 is a proto-oncogene which encodes for the serine/threonine kinase of the same name. The pim-1 oncogene was first described in relation to murine T-cell lymphomas, as it was the locus most frequently activated by the Moloney murine leukemia virus.[8] Subsequently, the oncogene has been implicated in multiple human cancers, including prostate cancer, acute myeloid leukemia and other hematopoietic malignancies.[9] Primarily expressed in spleen, thymus, bone marrow, prostate, oral epithelial, hippocampus and fetal liver cells, Pim-1 has also been found to be highly expressed in cell cultures isolated from human tumors.[8] Pim-1 is mainly involved in cell cycle progression, apoptosis and transcriptional activation, as well as more general signal transduction pathways.[8] Pim-1's role in oncogenic signalling has led to it becoming a widely studied target in cancer research, with numerous drug candidates under investigation which target it.[10][11]


Located on chromosome 6 (6p21.2), the gene encompasses 5Kb of DNA, including 6 exons and 5 introns. Expression of Pim-1 has been shown to be regulated by the JAK/STAT pathway. Direct binding of transcription factors STAT3 and STAT5 to the Pim-1 promoter results in the transcription of Pim-1.[8] The Pim-1 gene has been found to be conserved in dogs, cows, mice, rats, zebrafish and C. elegans. Pim-1 deficient mice have been shown to be phenotypically normal, indicating that there is redundancy in the function of this kinase.[8] In fact, sequence homology searches have shown that two other Pim-1-like kinases, Pim-2 and Pim-3, are structurally and functionally similar.[8] The Pim-1 gene encodes has multiple translation initiation sites, resulting in two proteins of 34 and 44kD.[8]

Protein structure

Human, murine and rat Pim-1 contain 313 amino acids, and have a 94 – 97% amino acid identity.[8] The active site of the protein, ranging from amino acids 38-290, is composed of several conserved motifs, including a glycine loop motif, a phosphate binding site and a proton acceptor site.[8] Modification of the protein at amino acid 67 (lysine to methionine) results in the inactivation of the kinase.[8]

Activation and stabilization

Pim-1 is primarily involved in cytokine signaling, and has been implicated in many signal transduction pathways. Because Pim-1 transcription is initiated by STAT3 and STAT5, its production is regulated by the cytokines that regulate the STAT pathway, or STAT factors. These include interleukins (IL-2, IL-3,IL-5, IL-6, IL-7, IL12, IL-15), prolactin, TNFα, EGF and IFNγ, among others.[8] Pim-1 itself can bind to negative regulators of the JAK/STAT pathway, resulting in a negative feedback loop.

Although little is known about the post-transcriptional modifications of Pim-1, it has been hypothesized that Hsp90 is responsible for the folding and stabilization of Pim-1, although the exact mechanism has yet to be discovered.[8] Furthermore, the serine/threonine phosphatase PP2 has been shown to degrade Pim-1.


PIM1 has been shown to interact with:

Other known substrates/binding partners of Pim-1 include proteins involved in transcription regulation (nuclear adaptor protein p100, HP-1, PAP-1 and TRAF2 / SNX6), and regulation of the JAK/STAT pathway (SOCS1 and SOCS3).[8] Furthermore, Pim-1 has been shown to be a cofactor for c-Myc, a transcription factor believed to regulate 15% of all genes, and their synergy has been in prostate tumorigenesis.[20]

Pim-1 is able to phosphorylate many targets, including itself. Many of its targets are involved in cell cycle regulation.



Clinical implications

Pim-1 is directly involved in the regulation of cell cycle progression and apoptosis, and has been implicated in numerous cancers including prostate cancer, Burkitt's lymphoma and oral cancer, as well as numerous hematopoietic lymphomas. Single nucleotide polymorphisms in the Pim-1 gene have been associated with increased risk for lung cancer in Korean patients, and have also been found in diffuse large cell lymphomas.[21] As well as showing useful activity against a range of cancers,[11] PIM kinase inhibitors have also been suggested as possible treatments for Alzheimer's disease.[22] PIM expression is sufficient to drive resistance to anti-angiogenic agents in prostate and colon cancer models, although the mechanism is not fully elucidated.[23] It has been suggested that a co-targeted therapeutic approach to inhibition of Pim-1 in cancer may be preferable, with suggested co-targets including the PI3K pathway and more.[10] PIM1 expression was found to be elevated during aging and to contribute to the development of pulmonary fibrosis.[24]


A large number of small molecule inhibitors of PIM1 have been developed. Clinical trial results so far have showed promising anti-cancer activity, but side effects due to insufficient selectivity have proved problematic and research continues to find more potent and selective inhibitors for this target.[25][26][27][28][29][30][31][10][11]



  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000137193 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000024014 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ "Entrez Gene: PIM1 pim-1 oncogene".
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  7. ^ Meeker TC, Nagarajan L, ar-Rushdi A, Rovera G, Huebner K, Croce CM (June 1987). "Characterization of the human PIM-1 gene: a putative proto-oncogene coding for a tissue specific member of the protein kinase family". Oncogene Research. 1 (1): 87–101. PMID 3329711.
  8. ^ a b c d e f g h i j k l m n o p q r Bachmann M, Möröy T (April 2005). "The serine/threonine kinase Pim-1". The International Journal of Biochemistry & Cell Biology. 37 (4): 726–30. doi:10.1016/j.biocel.2004.11.005. PMID 15694833.
  9. ^ "Pim-1 Oncogene". Retrieved 2015-12-14.
  10. ^ a b c Luszczak S, Kumar C, Sathyadevan VK, Simpson BS, Gately KA, Whitaker HC, Heavey S (2020). "PIM kinase inhibition: co-targeted therapeutic approaches in prostate cancer". Signal Transduction and Targeted Therapy. 5: 7. doi:10.1038/s41392-020-0109-y. PMC 6992635. PMID 32025342.
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  17. ^ Wang Z, Bhattacharya N, Mixter PF, Wei W, Sedivy J, Magnuson NS (December 2002). "Phosphorylation of the cell cycle inhibitor p21Cip1/WAF1 by Pim-1 kinase". Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 1593 (1): 45–55. doi:10.1016/S0167-4889(02)00347-6. PMID 12431783.
  18. ^ Leverson JD, Koskinen PJ, Orrico FC, Rainio EM, Jalkanen KJ, Dash AB, Eisenman RN, Ness SA (October 1998). "Pim-1 kinase and p100 cooperate to enhance c-Myb activity". Molecular Cell. 2 (4): 417–25. doi:10.1016/S1097-2765(00)80141-0. PMID 9809063.
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  21. ^ Kim DS, Sung JS, Shin ES, Ryu JS, Choi IK, Park KH, Park Y, Kim EB, Park SJ, Kim YH (December 2008). "Association of single nucleotide polymorphisms in PIM-1 gene with the risk of Korean lung cancer". Cancer Research and Treatment. 40 (4): 190–6. doi:10.4143/crt.2008.40.4.190. PMC 2697471. PMID 19688129.
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Further reading