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PMID: 12869584 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

The serine/threonine kinase Pim-2 is a transcriptionally regulated apoptotic inhibitor.

Genes & development ·Vol. 17 ·No. 15 ·2003-08-01 ·Pages 1841-54

Fox CJ, Hammerman PS, Cinalli RM, Master SR, Chodosh LA, Thompson CB

Abstract

Growth factor withdrawal results in the termination of factor-dependent transcription. One transcript that declines rapidly following growth factor deprivation of hematopoietic cells is the serine/threonine kinase pim-2. When constitutively expressed, Pim-2 conferred long-term resistance to a variety of apoptotic stimuli including growth factor withdrawal and endogenous levels of Pim-2 contributed to growth factor-mediated apoptotic resistance. Pim-2 expression maintained cell size and mitochondrial potential independently of the PI3K/Akt/TOR pathway. Pim-2-dependent maintenance of cell size and survival correlated with its ability to maintain rapamycin-resistant phosphorylation of the translational repressor 4E-BP1 and phosphorylation of the BH3 protein BAD. These results establish Pim-2 as a direct link between growth factor-induced transcription and a novel, kinase-dependent pathway that promotes cell-autonomous survival.

MeSH Terms
Animals Antibiotics, Antineoplastic/pharmacology Apoptosis Blotting, Northern Blotting, Western Cell Division Cell Line Cell Survival Dose-Response Relationship, Drug Flow Cytometry Gene Expression Regulation Genetic Vectors Glucose/metabolism,pharmacology Interleukin-3/metabolism Lactates/metabolism Membrane Potentials Mice Mitochondria/metabolism Oligonucleotide Array Sequence Analysis Phenotype Phosphorylation Plasmids/metabolism Protein Serine-Threonine Kinases Proto-Oncogene Proteins/metabolism,physiology Recombinant Proteins/metabolism Signal Transduction Sirolimus/pharmacology Staurosporine/pharmacology Thapsigargin/pharmacology Time Factors Transcription, Genetic Transgenes
Chemicals
Antibiotics, Antineoplastic Interleukin-3 Lactates Pim2 protein, mouse Proto-Oncogene Proteins Recombinant Proteins Thapsigargin Protein Serine-Threonine Kinases Staurosporine Glucose Sirolimus
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Fox Casey J
Abramson Family Cancer Research Institute, Philadelphia, Pennsylvania 19104, USA.
Hammerman Peter S
Cinalli Ryan M
Master Stephen R
Chodosh Lewis A
Thompson Craig B
References (50)
50 references, click to expand
  1. Identification of heterologous translocation partner genes fused to the BCL6 gene in diffuse large B-cell lymphomas: 5'-RACE and LA - PCR analyses of biopsy samples.
    Oncogene. 1999 Dec 23;18(56):7994-9 PMID: 10637510
  2. Pim-2 transgene induces lymphoid tumors, exhibiting potent synergy with c-myc.
    Oncogene. 1997 Sep 4;15(10):1133-41 PMID: 9294606
  3. Pim-1 kinase protects hematopoietic FDC cells from genotoxin-induced death.
    Oncogene. 2000 Jul 27;19(32):3684-92 PMID: 10951575
  4. Fos family members: regulation, structure and role in oncogenic transformation.
    Histol Histopathol. 2000 Jul;15(3):921-8 PMID: 10963134
  5. Neurosteroid analogues. 8. Structure-activity studies of N-acylated 17a-aza-D-homosteroid analogues of the anesthetic steroids (3alpha, 5alpha)- and (3alpha,5beta)-3-hydroxypregnan-20-one.
    J Med Chem. 2000 Aug 24;43(17):3201-4 PMID: 10966737
  6. In the absence of extrinsic signals, nutrient utilization by lymphocytes is insufficient to maintain either cell size or viability.
    Mol Cell. 2000 Sep;6(3):683-92 PMID: 11030347
  7. Akt and Bcl-xL promote growth factor-independent survival through distinct effects on mitochondrial physiology.
    J Biol Chem. 2001 Apr 13;276(15):12041-8 PMID: 11278698
  8. Pim-1 negatively regulates the activity of PTP-U2S phosphatase and influences terminal differentiation and apoptosis of monoblastoid leukemia cells.
    Arch Biochem Biophys. 2001 Jun 1;390(1):9-18 PMID: 11368509
  9. Novel NEMO/IkappaB kinase and NF-kappa B target genes at the pre-B to immature B cell transition.
    J Biol Chem. 2001 May 25;276(21):18579-90 PMID: 11279141
  10. Delineation of prognostic biomarkers in prostate cancer.
    Nature. 2001 Aug 23;412(6849):822-6 PMID: 11518967
  11. Spotting prostate cancer.
    Trends Mol Med. 2001 Oct;7(10):432 PMID: 11597508
  12. Microarray analysis of eosinophils reveals a number of candidate survival and apoptosis genes.
    Am J Respir Cell Mol Biol. 2001 Oct;25(4):425-33 PMID: 11694447
  13. Potential cellular signatures of viral infections in human hematopoietic cells.
    Dis Markers. 2001;17(3):173-8 PMID: 11790884
  14. The protein kinase B/Akt signalling pathway in human malignancy.
    Cell Signal. 2002 May;14(5):381-95 PMID: 11882383
  15. Translational control of cell fate: availability of phosphorylation sites on translational repressor 4E-BP1 governs its proapoptotic potency.
    Mol Cell Biol. 2002 Apr;22(8):2853-61 PMID: 11909977
  16. Genes preferentially induced by depolarization after concussive brain injury: effects of age and injury severity.
    J Neurotrauma. 2002 Apr;19(4):387-402 PMID: 11990346
  17. The conformational plasticity of protein kinases.
    Cell. 2002 May 3;109(3):275-82 PMID: 12015977
  18. The proto-oncogene c-myc in hematopoietic development and leukemogenesis.
    Oncogene. 2002 May 13;21(21):3414-21 PMID: 12032779
  19. Akt maintains cell size and survival by increasing mTOR-dependent nutrient uptake.
    Mol Biol Cell. 2002 Jul;13(7):2276-88 PMID: 12134068
  20. Bcl-X(L) affects Ca(2+) homeostasis by altering expression of inositol 1,4,5-trisphosphate receptors.
    Proc Natl Acad Sci U S A. 2002 Jul 23;99(15):9830-5 PMID: 12118121
  21. Molecular portraits of B cell lineage commitment.
    Proc Natl Acad Sci U S A. 2002 Jul 23;99(15):10014-9 PMID: 12119411
  22. Regulation of the FoxO family of transcription factors by phosphatidylinositol-3 kinase-activated signaling.
    Arch Biochem Biophys. 2002 Jul 15;403(2):292-8 PMID: 12139979
  23. Identification of downstream genes up-regulated by the tumor necrosis factor family member TALL-1.
    J Leukoc Biol. 2002 Aug;72(2):410-6 PMID: 12149433
  24. Persistent parity-induced changes in growth factors, TGF-beta3, and differentiation in the rodent mammary gland.
    Mol Endocrinol. 2002 Sep;16(9):2034-51 PMID: 12198241
  25. A tool coming of age: thapsigargin as an inhibitor of sarco-endoplasmic reticulum Ca(2+)-ATPases.
    Trends Pharmacol Sci. 1998 Apr;19(4):131-5 PMID: 9612087
  26. KID-1, a protein kinase induced by depolarization in brain.
    J Biol Chem. 1998 Jun 26;273(26):16535-43 PMID: 9632723
  27. Pim-1 kinase and p100 cooperate to enhance c-Myb activity.
    Mol Cell. 1998 Oct;2(4):417-25 PMID: 9809063
  28. Pim kinase expression is induced by LTP stimulation and required for the consolidation of enduring LTP.
    EMBO J. 1999 Jun 15;18(12):3359-69 PMID: 10369676
  29. Physical and functional interactions between Pim-1 kinase and Cdc25A phosphatase. Implications for the Pim-1-mediated activation of the c-Myc signaling pathway.
    J Biol Chem. 1999 Jun 25;274(26):18659-66 PMID: 10373478
  30. The PIM-1 serine kinase prolongs survival and inhibits apoptosis-related mitochondrial dysfunction in part through a bcl-2-dependent pathway.
    Oncogene. 1999 Jul 8;18(27):4022-31 PMID: 10435626
  31. Interaction of radicicol with members of the heat shock protein 90 family of molecular chaperones.
    Mol Endocrinol. 1999 Sep;13(9):1435-48 PMID: 10478836
  32. Translation initiation factor modifications and the regulation of protein synthesis in apoptotic cells.
    Cell Death Differ. 2000 Jul;7(7):603-15 PMID: 10889505
  33. A molecular compendium of genes expressed in multiple myeloma.
    Blood. 2002 Sep 15;100(6):2175-86 PMID: 12200383
  34. High-throughput retroviral tagging to identify components of specific signaling pathways in cancer.
    Nat Genet. 2002 Sep;32(1):153-9 PMID: 12185366
  35. The Bcl2 family: regulators of the cellular life-or-death switch.
    Nat Rev Cancer. 2002 Sep;2(9):647-56 PMID: 12209154
  36. c-MYC: more than just a matter of life and death.
    Nat Rev Cancer. 2002 Oct;2(10):764-76 PMID: 12360279
  37. Akt forms an intracellular complex with heat shock protein 90 (Hsp90) and Cdc37 and is destabilized by inhibitors of Hsp90 function.
    J Biol Chem. 2002 Oct 18;277(42):39858-66 PMID: 12176997
  38. Two TOR complexes, only one of which is rapamycin sensitive, have distinct roles in cell growth control.
    Mol Cell. 2002 Sep;10(3):457-68 PMID: 12408816
  39. Proviral activation of the putative oncogene Pim-1 in MuLV induced T-cell lymphomas.
    EMBO J. 1985 Jul;4(7):1793-8 PMID: 2992942
  40. Evidence for the involvement of pim-2, a new common proviral insertion site, in progression of lymphomas.
    EMBO J. 1989 Mar;8(3):743-8 PMID: 2721500
  41. The human protooncogene product p33pim is expressed during fetal hematopoiesis and in diverse leukemias.
    Proc Natl Acad Sci U S A. 1989 Nov;86(22):8857-61 PMID: 2682662
  42. Mice bearing the E mu-myc and E mu-pim-1 transgenes develop pre-B-cell leukemia prenatally.
    Mol Cell Biol. 1991 Feb;11(2):1176-9 PMID: 1990273
  43. E mu N- and E mu L-myc cooperate with E mu pim-1 to generate lymphoid tumors at high frequency in double-transgenic mice.
    Oncogene. 1991 Nov;6(11):1941-8 PMID: 1658705
  44. A specific inhibitor of phosphatidylinositol 3-kinase, 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002).
    J Biol Chem. 1994 Feb 18;269(7):5241-8 PMID: 8106507
  45. Regulation of the interleukin-3 (IL-3) receptor by IL-3 in the fetal liver-derived FL5.12 cell line.
    Blood. 1994 May 1;83(9):2459-68 PMID: 8167335
  46. Proviral tagging in E mu-myc transgenic mice lacking the Pim-1 proto-oncogene leads to compensatory activation of Pim-2.
    EMBO J. 1995 Jun 1;14(11):2536-44 PMID: 7781606
  47. Staurosporine, a potentially important gift from a microorganism.
    J Antibiot (Tokyo). 1995 Jul;48(7):535-48 PMID: 7649849
  48. Regulation of cell division cycle progression by bcl-2 expression: a potential mechanism for inhibition of programmed cell death.
    J Exp Med. 1996 May 1;183(5):2219-26 PMID: 8642331
  49. The cell death inhibitor Bcl-2 and its homologues influence control of cell cycle entry.
    EMBO J. 1996 Dec 16;15(24):6979-90 PMID: 9003774
  50. Complementation tagging of cooperating oncogenes in knockout mice.
    Semin Cancer Biol. 1996 Oct;7(5):299-306 PMID: 9110407
Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.1105003
Published
2003-08-01
Epub
2003-00-17
Pages
1841-54
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC196230
Subset
IM
Corrections
CommentIn
PMID: 12897050
External Links
PubMed source DOI: 10.1101/gad.1105003 PMC Full Text View journal details
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