proto oncogene proteins c pim 1


Summary: Serine-threonine protein kinases that relay signals from CYTOKINE RECEPTORS and are involved in control of CELL GROWTH PROCESSES; CELL DIFFERENTIATION; and APOPTOSIS.

Top Publications

  1. Wang J, Kim J, Roh M, Franco O, Hayward S, Wills M, et al. Pim1 kinase synergizes with c-MYC to induce advanced prostate carcinoma. Oncogene. 2010;29:2477-87 pubmed publisher
    ..These results directly show functional cooperativity between c-MYC and PIM1 in prostate tumorigenesis in vivo and support efforts for targeting PIM1 in prostate cancer. ..
  2. Guo G, Qiu X, Wang S, Rothman P, Wang Z, Chen Y, et al. Oncogenic E17K mutation in the pleckstrin homology domain of AKT1 promotes v-Abl-mediated pre-B-cell transformation and survival of Pim-deficient cells. Oncogene. 2010;29:3845-53 pubmed publisher
    ..In addition, AKT1(E17K) delays loss of Pim-1 and Pim-2 protein levels on v-Abl inactivation, which suggests that there exists reciprocal signaling between AKT and Pim in v-Abl transformants. ..
  3. Li J, Hu X, Loveland B, Xing P. Pim-1 expression and monoclonal antibody targeting in human leukemia cell lines. Exp Hematol. 2009;37:1284-94 pubmed publisher
    ..Targeting Pim-1 with monoclonal antibody could be explored for the treatment of leukemia and may represent a novel strategy to overcome drug resistance. ..
  4. Bullock A, Russo S, Amos A, Pagano N, Bregman H, Debreczeni J, et al. Crystal structure of the PIM2 kinase in complex with an organoruthenium inhibitor. PLoS ONE. 2009;4:e7112 pubmed publisher
    ..Please note that a web plugin is required to access this enhanced functionality. Instructions for the installation and use of the web plugin are available in Text S1. ..
  5. Morwick T. Pim kinase inhibitors: a survey of the patent literature. Expert Opin Ther Pat. 2010;20:193-212 pubmed publisher
    ..Ongoing studies will help define applications for these inhibitors in the treatment of Pim-associated human diseases. ..
  6. Muraski J, Fischer K, Wu W, Cottage C, Quijada P, Mason M, et al. Pim-1 kinase antagonizes aspects of myocardial hypertrophy and compensation to pathological pressure overload. Proc Natl Acad Sci U S A. 2008;105:13889-94 pubmed publisher
    ..These data support a pivotal role for Pim-1 in modulation of hypertrophy by impacting responses on molecular, cellular, and organ levels. ..
  7. Sliman F, Blairvacq M, Durieu E, Meijer L, Rodrigo J, Desmaele D. Identification and structure-activity relationship of 8-hydroxy-quinoline-7-carboxylic acid derivatives as inhibitors of Pim-1 kinase. Bioorg Med Chem Lett. 2010;20:2801-5 pubmed publisher
    ..Molecular modeling indicated that interaction of this scaffold with Asp186 and Lys67 residues within the ATP-binding pocket might be responsible for the kinase inhibitory potency. ..
  8. Warnecke Eberz U, Bollschweiler E, Drebber U, Metzger R, Baldus S, Holscher A, et al. Prognostic impact of protein overexpression of the proto-oncogene PIM-1 in gastric cancer. Anticancer Res. 2009;29:4451-5 pubmed
    ..Up-regulation of PIM-1 oncogene might be a tumor marker for gastric cancer. The correlation of PIM-1 overexpression in gastric glands with formation of lymph node metastases and survival proposes a prognostic role in gastric cancer. ..
  9. Kim J, Roh M, Abdulkadir S. Pim1 promotes human prostate cancer cell tumorigenicity and c-MYC transcriptional activity. BMC Cancer. 2010;10:248 pubmed publisher
    ..Pim1 promotes tumorigenicity at least in part by enhancing c-MYC transcriptional activity. We also made the novel discovery that treatment of cells with the c-MYC inhibitor 10058-F4 leads to a reduction in Pim1 protein levels. ..

More Information


  1. Fröjmark A, Badhai J, Klar J, Thuveson M, Schuster J, Dahl N. Cooperative effect of ribosomal protein s19 and Pim-1 kinase on murine c-Myc expression and myeloid/erythroid cellularity. J Mol Med (Berl). 2010;88:39-46 pubmed publisher
    ..Our findings suggest that combined Rps19 insufficiency and Pim-1 deficiency promote murine myeloid cell growth through a deregulation of c-Myc and a simultaneous up-regulation of anti-apoptotic Bcl proteins. ..
  2. Tao Z, Hasvold L, Leverson J, Han E, Guan R, Johnson E, et al. Discovery of 3H-benzo[4,5]thieno[3,2-d]pyrimidin-4-ones as potent, highly selective, and orally bioavailable inhibitors of the human protooncogene proviral insertion site in moloney murine leukemia virus (PIM) kinases. J Med Chem. 2009;52:6621-36 pubmed publisher
    ..ADME profiling of 14j suggested a long half-life in both human and mouse liver microsomes, good permeability, modest protein binding, and no CYP inhibition below 20 muM concentration. ..
  3. Zemskova M, Lilly M, Lin Y, Song J, Kraft A. p53-dependent induction of prostate cancer cell senescence by the PIM1 protein kinase. Mol Cancer Res. 2010;8:1126-41 pubmed publisher
    ..Based on these results, PIM1 will have its most profound effects on tumorigenesis in situations where the senescence response is inactivated. ..
  4. Lin Y, Beharry Z, Hill E, Song J, Wang W, Xia Z, et al. A small molecule inhibitor of Pim protein kinases blocks the growth of precursor T-cell lymphoblastic leukemia/lymphoma. Blood. 2010;115:824-33 pubmed publisher
    ..Our data suggest that inhibition of the Pim protein kinases may be developed as a therapeutic strategy for the treatment of pre-T-LBL. ..
  5. Stumpner J, Redel A, Kellermann A, Lotz C, Blomeyer C, Smul T, et al. Differential role of Pim-1 kinase in anesthetic-induced and ischemic preconditioning against myocardial infarction. Anesthesiology. 2009;111:1257-64 pubmed publisher
    ..These data suggest that Pim-1 kinase mediates at least in part desflurane-induced preconditioning and IPC against myocardial infarction in mice. ..
  6. Nihira K, Ando Y, Yamaguchi T, Kagami Y, Miki Y, Yoshida K. Pim-1 controls NF-kappaB signalling by stabilizing RelA/p65. Cell Death Differ. 2010;17:689-98 pubmed publisher
    ..These findings provide a model in which Pim-1 phosphorylation of RelA/p65 at Ser276 allows defense against ubiquitin-mediated degradation and whereby exerts activation of NF-kappaB signalling. ..
  7. López Ramos M, Prudent R, Moucadel V, Sautel C, Barette C, Lafanechere L, et al. New potent dual inhibitors of CK2 and Pim kinases: discovery and structural insights. FASEB J. 2010;24:3171-85 pubmed publisher
    ..This work highlights that 2 functionally related kinases from different kinome branches display exquisite sensitivity to a common inhibitor. ..
  8. Nga M, Swe N, Chen K, Shen L, Lilly M, Chan S, et al. PIM-1 kinase expression in adipocytic neoplasms: diagnostic and biological implications. Int J Exp Pathol. 2010;91:34-43 pubmed publisher
    ..Our results indicate that the expression of PIM-1 in adipose tissue may be a useful marker of adipocytic differentiation, in particular if the staining is both of high intensity and present in a unique, vacuolar pattern. ..
  9. Chen J, Kobayashi M, Darmanin S, Qiao Y, Gully C, Zhao R, et al. Hypoxia-mediated up-regulation of Pim-1 contributes to solid tumor formation. Am J Pathol. 2009;175:400-11 pubmed publisher
    ..Together, our studies indicate that Pim-1 plays a distinct role in solid tumor formation in vivo, implying that Pim-1 may be a novel target for cancer therapy. ..
  10. He H, Bi X, Zheng Z, Dai Q, Han Z, Liang Y, et al. Real-time quantitative RT-PCR assessment of PIM-1 and hK2 mRNA expression in benign prostate hyperplasia and prostate cancer. Med Oncol. 2009;26:303-8 pubmed publisher
  11. Cheng F, Weidner Glunde M, Varjosalo M, Rainio E, Lehtonen A, Schulz T, et al. KSHV reactivation from latency requires Pim-1 and Pim-3 kinases to inactivate the latency-associated nuclear antigen LANA. PLoS Pathog. 2009;5:e1000324 pubmed publisher
  12. Miyamoto S, Rubio M, Sussman M. Nuclear and mitochondrial signalling Akts in cardiomyocytes. Cardiovasc Res. 2009;82:272-85 pubmed publisher
  13. Peltola K, Hollmen M, Maula S, Rainio E, Ristamaki R, Luukkaa M, et al. Pim-1 kinase expression predicts radiation response in squamocellular carcinoma of head and neck and is under the control of epidermal growth factor receptor. Neoplasia. 2009;11:629-36 pubmed
    ..These results suggest that irradiation-induced activation of EGFR upregulates Pim-1, and Pim-1 may be used as a novel predictive marker of radiation response in patients with squamocellular cancers of head and neck. ..
  14. Cen B, Mahajan S, Zemskova M, Beharry Z, Lin Y, Cramer S, et al. Regulation of Skp2 levels by the Pim-1 protein kinase. J Biol Chem. 2010;285:29128-37 pubmed publisher
    ..Consistent with these observations, we show that Pim-1 is able to cooperate with Skp2 to signal S phase entry. Our data reveal a novel Pim-1 kinase-dependent signaling pathway that plays a crucial role in cell cycle regulation. ..
  15. Li Y, Wang Y, Taniguchi T, Kawakami T, Baba T, Ishibashi H, et al. Identification of stemonamide synthetic intermediates as a novel potent anticancer drug with an apoptosis-inducing ability. Int J Cancer. 2010;127:474-84 pubmed publisher
    ..These observations indicate that the chemicals and its related compounds may be effective for the treatment of tumors of endoderm-derived organs, particularly the pancreas. ..
  16. Badham H, Renaud S, Wan J, Winn L. Benzene-initiated oxidative stress: Effects on embryonic signaling pathways. Chem Biol Interact. 2010;184:218-21 pubmed publisher
    ..Further studies evaluating the reason for this gender difference are ongoing. ..
  17. Chen L, Balakrishnan K, Gandhi V. Inflammation and survival pathways: chronic lymphocytic leukemia as a model system. Biochem Pharmacol. 2010;80:1936-45 pubmed publisher
    ..Vigorous efforts are being made to create small molecules that affect these proteins directly or indirectly. Several of these pharmacological inhibitors are in early clinical trials for patients with hematological malignancies. ..
  18. Akue Gedu R, Nauton L, Thery V, Bain J, Cohen P, Anizon F, et al. Synthesis, Pim kinase inhibitory potencies and in vitro antiproliferative activities of diversely substituted pyrrolo[2,3-a]carbazoles. Bioorg Med Chem. 2010;18:6865-73 pubmed publisher
    ..Moreover, molecular docking studies were performed to explain the enhanced inhibitory activity of the most active compound 3d. ..
  19. Katare R, Caporali A, Oikawa A, Meloni M, Emanueli C, Madeddu P. Vitamin B1 analog benfotiamine prevents diabetes-induced diastolic dysfunction and heart failure through Akt/Pim-1-mediated survival pathway. Circ Heart Fail. 2010;3:294-305 pubmed publisher
    ..Thus, BFT merits attention for application in clinical practice. ..
  20. van der Poel H, Zevenhoven J, Bergman A. Pim1 regulates androgen-dependent survival signaling in prostate cancer cells. Urol Int. 2010;84:212-20 pubmed publisher
    ..Pim1 overexpression increased AR transcriptional activity in a ligand-dependent manner in prostate cancer cell lines, resulting in enhanced cell survival at castrate levels of androgen. ..
  21. Xie Y, Burcu M, Linn D, Qiu Y, Baer M. Pim-1 kinase protects P-glycoprotein from degradation and enables its glycosylation and cell surface expression. Mol Pharmacol. 2010;78:310-8 pubmed publisher
    ..Pim-1 inhibitors are entering clinical trials and may provide a novel approach to abrogating drug resistance. ..
  22. Zhang Y, Parsanejad M, Huang E, Qu D, Aleyasin H, Rousseaux M, et al. Pim-1 kinase as activator of the cell cycle pathway in neuronal death induced by DNA damage. J Neurochem. 2010;112:497-510 pubmed publisher
    ..Taken together, our results demonstrate that Pim-1 kinase plays a central role in DNA damage-evoked neuronal death by regulating aberrant neuronal cell cycle activation. ..
  23. Preuss I, Hildebrand D, Orth J, Aktories K, Kubatzky K. Pasteurella multocida toxin is a potent activator of anti-apoptotic signalling pathways. Cell Microbiol. 2010;12:1174-85 pubmed publisher
    ..Our data indicate that PMT is a highly potent anti-apoptotic agent, which supports the view of a carcinogenic potential of the toxin...
  24. Sussman M. Mitochondrial integrity: preservation through Akt/Pim-1 kinase signaling in the cardiomyocyte. Expert Rev Cardiovasc Ther. 2009;7:929-38 pubmed publisher
    ..This review focuses on two emerging pathways that mediate preservation of mitochondrial function downstream of Akt: hexokinase and Pim-1 kinase. ..
  25. Beharry Z, Zemskova M, Mahajan S, Zhang F, Ma J, Xia Z, et al. Novel benzylidene-thiazolidine-2,4-diones inhibit Pim protein kinase activity and induce cell cycle arrest in leukemia and prostate cancer cells. Mol Cancer Ther. 2009;8:1473-83 pubmed publisher
    ..Thus, these agents represent novel Pim inhibitors and point to an important role for the Pim protein kinases in cell cycle control in multiple types of cancer cells. ..
  26. Vu H, Xinh P, Kano Y, Tokunaga K, Sato Y. The juxtamembrane domain in ETV6/FLT3 is critical for PIM-1 up-regulation and cell proliferation. Biochem Biophys Res Commun. 2009;383:308-13 pubmed publisher
  27. Akue Gedu R, Rossignol E, Azzaro S, Knapp S, Filippakopoulos P, Bullock A, et al. Synthesis, kinase inhibitory potencies, and in vitro antiproliferative evaluation of new Pim kinase inhibitors. J Med Chem. 2009;52:6369-81 pubmed publisher
    ..The structure revealed a non-ATP mimetic binding mode with no hydrogen bonds formed with the kinase hinge region and explained the selectivity of pyrrolo[2,3-a]carbazole derivatives for Pim kinases. ..
  28. Guo R, Zhong L, Ren J. Overexpression of aldehyde dehydrogenase-2 attenuates chronic alcohol exposure-induced apoptosis, change in Akt and Pim signalling in liver. Clin Exp Pharmacol Physiol. 2009;36:463-8 pubmed publisher
    ..4. Collectively, the results suggest that ALDH2 may effectively ameliorate alcohol-induced hepatic apoptosis and changes in Akt as well as Pim signalling. ..
  29. Doudou S, Sharma R, Henchman R, Sheppard D, Burton N. Inhibitors of PIM-1 kinase: a computational analysis of the binding free energies of a range of imidazo [1,2-b] pyridazines. J Chem Inf Model. 2010;50:368-79 pubmed publisher
    ..The potential of mean force for the displacement of the glycine-rich phosphate binding loop (P-loop) has also been estimated and shown to be an important feature in the binding of these ligands. ..
  30. Grey R, Pierce A, Bemis G, Jacobs M, Moody C, Jajoo R, et al. Structure-based design of 3-aryl-6-amino-triazolo[4,3-b]pyridazine inhibitors of Pim-1 kinase. Bioorg Med Chem Lett. 2009;19:3019-22 pubmed publisher
    ..This resulted in compound 29, a selective, soluble and permeable inhibitor of Pim-1. ..
  31. Eiring A, Harb J, Neviani P, Garton C, Oaks J, Spizzo R, et al. miR-328 functions as an RNA decoy to modulate hnRNP E2 regulation of mRNA translation in leukemic blasts. Cell. 2010;140:652-65 pubmed publisher
    ..Altogether, these data reveal the dual ability of a microRNA to control cell fate both through base pairing with mRNA targets and through a decoy activity that interferes with the function of regulatory proteins. ..
  32. Borillo G, Mason M, Quijada P, Völkers M, Cottage C, McGregor M, et al. Pim-1 kinase protects mitochondrial integrity in cardiomyocytes. Circ Res. 2010;106:1265-74 pubmed publisher
  33. Wozniak M, Villuendas R, Bischoff J, Aparicio C, Martinez Leal J, de la Cueva P, et al. Vorinostat interferes with the signaling transduction pathway of T-cell receptor and synergizes with phosphoinositide-3 kinase inhibitors in cutaneous T-cell lymphoma. Haematologica. 2010;95:613-21 pubmed publisher
    ..Additionally, we showed that combination therapies involving histone deacetylase inhibitors and inhibitors of PI3K are potentially efficacious for the treatment of cutaneous T-cell lymphoma. ..
  34. Cottage C, Bailey B, Fischer K, Avitabile D, Avitable D, Collins B, et al. Cardiac progenitor cell cycling stimulated by pim-1 kinase. Circ Res. 2010;106:891-901 pubmed publisher
    ..These findings define a mechanistic basis for enhanced myocardial regeneration in transgenic mice overexpressing Pim-1 kinase. ..
  35. Penna C, Perrelli M, Raimondo S, Tullio F, Merlino A, Moro F, et al. Postconditioning induces an anti-apoptotic effect and preserves mitochondrial integrity in isolated rat hearts. Biochim Biophys Acta. 2009;1787:794-801 pubmed publisher
    ..g. cytochrome c, iii) preserves the mitochondrial structure, and iv) limits the migration of phospho-Cx43 to mitochondria. ..
  36. Liu H, Wang N, Wang X, Li S. Overexpression of Pim-1 is associated with poor prognosis in patients with esophageal squamous cell carcinoma. J Surg Oncol. 2010;102:683-8 pubmed publisher
    ..010 and 0.001, respectively). These findings demonstrate that Pim-1 may be used as molecular marker for predicting the prognosis of patients with ESCC. ..
  37. Grundler R, Brault L, Gasser C, Bullock A, Dechow T, Woetzel S, et al. Dissection of PIM serine/threonine kinases in FLT3-ITD-induced leukemogenesis reveals PIM1 as regulator of CXCL12-CXCR4-mediated homing and migration. J Exp Med. 2009;206:1957-70 pubmed publisher
    ..Because CXCR4 also regulates homing and maintenance of cancer stem cells, PIM1 inhibitors may exert their antitumor effects in part by interfering with interactions with the microenvironment. ..
  38. Defranchi E, De Franchi E, Schalon C, Messa M, Onofri F, Benfenati F, et al. Binding of protein kinase inhibitors to synapsin I inferred from pair-wise binding site similarity measurements. PLoS ONE. 2010;5:e12214 pubmed publisher
    ..More generally, the data also demonstrate that cross-reactivity with various targets may be detected by systematic pair-wise similarity measurement of ligand-annotated binding sites. ..
  39. Iadevaia V, Caldarola S, Biondini L, Gismondi A, Karlsson S, Dianzani I, et al. PIM1 kinase is destabilized by ribosomal stress causing inhibition of cell cycle progression. Oncogene. 2010;29:5490-9 pubmed publisher
    ..Notably, restoring PIM1 level by transfection causes a recovery of cell growth. Our data indicate that PIM1 may act as a sensor for ribosomal stress independently of or in concert with the known p53-dependent mechanisms. ..
  40. Bailey B, Izarra A, Alvarez R, Fischer K, Cottage C, Quijada P, et al. Cardiac stem cell genetic engineering using the alphaMHC promoter. Regen Med. 2009;4:823-33 pubmed publisher
    ..Therapeutic genes controlled by the alphaMHC promoter can be engineered into and expressed in CSCs and cardiomyocyte progeny with the goal of improving the efficacy of cardiac stem cell therapy. ..
  41. Fischer K, Cottage C, Wu W, Din S, Gude N, Avitabile D, et al. Enhancement of myocardial regeneration through genetic engineering of cardiac progenitor cells expressing Pim-1 kinase. Circulation. 2009;120:2077-87 pubmed publisher
    ..Ex vivo gene delivery to enhance cellular survival, proliferation, and regeneration may overcome current limitations of stem cell-based therapeutic approaches. ..
  42. Mumenthaler S, Ng P, Hodge A, Bearss D, Berk G, Kanekal S, et al. Pharmacologic inhibition of Pim kinases alters prostate cancer cell growth and resensitizes chemoresistant cells to taxanes. Mol Cancer Ther. 2009;8:2882-93 pubmed publisher
    ..These findings support the idea that inhibiting Pim kinases, in combination with a chemotherapeutic agent, could play an important role in prostate cancer treatment by targeting the clinical problem of chemoresistance. ..
  43. Chen L, Redkar S, Bearss D, Wierda W, Gandhi V. Pim kinase inhibitor, SGI-1776, induces apoptosis in chronic lymphocytic leukemia cells. Blood. 2009;114:4150-7 pubmed publisher
    ..Consistent with a decline in new RNA synthesis, MCL-1 transcript levels were decreased after treatment with SGI-1776. These data suggest that SGI-1776 induces apoptosis in CLL and that the mechanism involves Mcl-1 reduction. ..
  44. Akagi T, Shih L, Ogawa S, Gerss J, Moore S, Schreck R, et al. Single nucleotide polymorphism genomic arrays analysis of t(8;21) acute myeloid leukemia cells. Haematologica. 2009;94:1301-6 pubmed publisher
    ..Importantly, prognostic analysis revealed that overall survival and event-free survival of individuals in Group B were significantly worse than those in Group A. ..
  45. Willert M, Augstein A, Poitz D, Schmeisser A, Strasser R, Braun Dullaeus R. Transcriptional regulation of Pim-1 kinase in vascular smooth muscle cells and its role for proliferation. Basic Res Cardiol. 2010;105:267-77 pubmed publisher
    ..Our findings help to understand the fundamental processes of vasculoproliferative diseases thus opening avenues for its prevention and treatment. ..
  46. Chen J, Kobayashi M, Darmanin S, Qiao Y, Gully C, Zhao R, et al. Pim-1 plays a pivotal role in hypoxia-induced chemoresistance. Oncogene. 2009;28:2581-92 pubmed publisher
    ..Our results demonstrate that Pim-1 is a pivotal regulator involved in hypoxia-induced chemoresistance. Targeting Pim-1 may improve the chemotherapeutic strategy for solid tumors. ..
  47. Zhang F, Beharry Z, Harris T, Lilly M, Smith C, Mahajan S, et al. PIM1 protein kinase regulates PRAS40 phosphorylation and mTOR activity in FDCP1 cells. Cancer Biol Ther. 2009;8:846-53 pubmed
    ..These results suggest that PIM1 regulates mTOR activity through phosphorylation of PRAS40. Thus, increases in mTOR activity mediated by the PIM protein kinase may have the potential to control cell growth. ..
  48. Qian K, Wang L, Cywin C, Farmer B, Hickey E, Homon C, et al. Hit to lead account of the discovery of a new class of inhibitors of Pim kinases and crystallographic studies revealing an unusual kinase binding mode. J Med Chem. 2009;52:1814-27 pubmed publisher
    ..Some interesting cross reactivity with casein kinase-2 was also identified, and structural features which may contribute to the association are discussed. ..