Edward V Prochownik

Summary

Affiliation: Children's Hospital of Pittsburgh
Country: USA

Publications

  1. ncbi request reprint Pag, a putative tumor suppressor, interacts with the Myc Box II domain of c-Myc and selectively alters its biological function and target gene expression
    Zhao Mei Mu
    Section of Hematology Oncology, The Children s Hospital of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA
    J Biol Chem 277:43175-84. 2002
  2. ncbi request reprint c-Myc: linking transformation and genomic instability
    Edward V Prochownik
    Division of Hematology Oncology, Children s Hospital of Pittsburgh, Pittsburgh, PA 15213, USA
    Curr Mol Med 8:446-58. 2008
  3. pmc Alterations in c-Myc phenotypes resulting from dynamin-related protein 1 (Drp1)-mediated mitochondrial fission
    M Sarin
    Division of Hematology Oncology, Children s Hospital of Pittburgh of UPMC, Pittsburgh, PA 15224, USA
    Cell Death Dis 4:e670. 2013
  4. ncbi request reprint The ever expanding role for c-Myc in promoting genomic instability
    Edward V Prochownik
    Section of Hematology Oncology, Children s Hospital of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA
    Cell Cycle 6:1024-9. 2007
  5. ncbi request reprint Functional and physical communication between oncoproteins and tumor suppressors
    E V Prochownik
    Section of Hematology Oncology, Children s Hospital of Pittsburgh, Rangos Research Center, Room 2100, 3460 Fifth Avenue, Pittsburgh, PA 15213, USA
    Cell Mol Life Sci 62:2438-59. 2005
  6. ncbi request reprint Onzin, a c-Myc-repressed target, promotes survival and transformation by modulating the Akt-Mdm2-p53 pathway
    Kenneth Rogulski
    Section of Hematology Oncology, Children s Hospital of Pittsburgh, Pittsburgh, PA 15213, USA
    Oncogene 24:7524-41. 2005
  7. pmc The c-Myc target glycoprotein1balpha links cytokinesis failure to oncogenic signal transduction pathways in cultured human cells
    Qian Wu
    Department of Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
    PLoS ONE 5:e10819. 2010
  8. pmc Modularity of the oncoprotein-like properties of platelet glycoprotein Ibalpha
    Youjun Li
    Section of Hematology Oncology, Children s Hospital of Pittsburgh Pittsburgh, Pennsylvania 15213, USA
    J Biol Chem 284:1410-8. 2009
  9. pmc Discovery of novel Myc-Max heterodimer disruptors with a three-dimensional pharmacophore model
    Gabriela Mustata
    Department of Computational Biology, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA
    J Med Chem 52:1247-50. 2009
  10. pmc Deregulation of common genes by c-Myc and its direct target, MT-MC1
    Kenneth R Rogulski
    Section of Hematology Oncology, Children s Hospital of Pittsburgh, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA 15213, USA
    Proc Natl Acad Sci U S A 102:18968-73. 2005

Collaborators

Detail Information

Publications44

  1. ncbi request reprint Pag, a putative tumor suppressor, interacts with the Myc Box II domain of c-Myc and selectively alters its biological function and target gene expression
    Zhao Mei Mu
    Section of Hematology Oncology, The Children s Hospital of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA
    J Biol Chem 277:43175-84. 2002
    ..These features, along with the previously identified interaction with c-Abl, provide support for the idea that Pag functions as a tumor suppressor...
  2. ncbi request reprint c-Myc: linking transformation and genomic instability
    Edward V Prochownik
    Division of Hematology Oncology, Children s Hospital of Pittsburgh, Pittsburgh, PA 15213, USA
    Curr Mol Med 8:446-58. 2008
    ....
  3. pmc Alterations in c-Myc phenotypes resulting from dynamin-related protein 1 (Drp1)-mediated mitochondrial fission
    M Sarin
    Division of Hematology Oncology, Children s Hospital of Pittburgh of UPMC, Pittsburgh, PA 15224, USA
    Cell Death Dis 4:e670. 2013
    ..The low intracellular ATP levels that are frequently seen in some tumors as a result of inadequate vascular perfusion could favor tumor survival by countering the pro-apoptotic tendencies of Myc overexpression...
  4. ncbi request reprint The ever expanding role for c-Myc in promoting genomic instability
    Edward V Prochownik
    Section of Hematology Oncology, Children s Hospital of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA
    Cell Cycle 6:1024-9. 2007
    ..These genome-altering properties of c-Myc suggest that they provide the protein with the ability to confer a "mutator phenotype" to cells in which its expression is deregulated...
  5. ncbi request reprint Functional and physical communication between oncoproteins and tumor suppressors
    E V Prochownik
    Section of Hematology Oncology, Children s Hospital of Pittsburgh, Rangos Research Center, Room 2100, 3460 Fifth Avenue, Pittsburgh, PA 15213, USA
    Cell Mol Life Sci 62:2438-59. 2005
    ....
  6. ncbi request reprint Onzin, a c-Myc-repressed target, promotes survival and transformation by modulating the Akt-Mdm2-p53 pathway
    Kenneth Rogulski
    Section of Hematology Oncology, Children s Hospital of Pittsburgh, Pittsburgh, PA 15213, USA
    Oncogene 24:7524-41. 2005
    ..This is reminiscent of the c-Myc --> p19(ARF)--mid R: Mdm2 pathway and might function as a complementary arm to ensure the proper cellular response to oncogenic and/or apoptotic stimuli...
  7. pmc The c-Myc target glycoprotein1balpha links cytokinesis failure to oncogenic signal transduction pathways in cultured human cells
    Qian Wu
    Department of Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
    PLoS ONE 5:e10819. 2010
    ..These results indicate that cytokinesis failure and tetraploidy in cancer cells are directly linked to cellular hyperproliferation via c-Myc induced overexpression of GpIbalpha...
  8. pmc Modularity of the oncoprotein-like properties of platelet glycoprotein Ibalpha
    Youjun Li
    Section of Hematology Oncology, Children s Hospital of Pittsburgh Pittsburgh, Pennsylvania 15213, USA
    J Biol Chem 284:1410-8. 2009
    ..Together, these results provide strong evidence that the domains of GpIbalpha mediating c-Myc-like functions are modular, genetically distinct, and independent of those involved in vWFR signaling...
  9. pmc Discovery of novel Myc-Max heterodimer disruptors with a three-dimensional pharmacophore model
    Gabriela Mustata
    Department of Computational Biology, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA
    J Med Chem 52:1247-50. 2009
    ..These studies demonstrate the applicability of pharmacophore modeling to the identification of novel and potentially more puissant inhibitors of the c-Myc oncoprotein...
  10. pmc Deregulation of common genes by c-Myc and its direct target, MT-MC1
    Kenneth R Rogulski
    Section of Hematology Oncology, Children s Hospital of Pittsburgh, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA 15213, USA
    Proc Natl Acad Sci U S A 102:18968-73. 2005
    ..Our results thus indicate that MT-MC1 target genes largely comprise a subset of those regulated by c-Myc. We propose that the properties imparted by MT-MC1 are the result of its control of a small and select c-Myc target gene population...
  11. pmc In vitro cytotoxicity and in vivo efficacy, pharmacokinetics, and metabolism of 10074-G5, a novel small-molecule inhibitor of c-Myc/Max dimerization
    Dana M Clausen
    Molecular Therapeutics Drug Discovery Program, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania 15213, USA
    J Pharmacol Exp Ther 335:715-27. 2010
    ..Our identification of 10074-G5 metabolites in mice will help design new, more metabolically stable small-molecule inhibitors of c-Myc...
  12. ncbi request reprint Regulation of reactive oxygen species, DNA damage, and c-Myc function by peroxiredoxin 1
    Rachel A Egler
    Department of Pediatrics, Section of Hematology Oncology, Children s Hospital of Pittsburgh, Rangos Research Center, 3460 Fifth Ave, USA
    Oncogene 24:8038-50. 2005
    ..prdx1-/- mice should be useful in studying the role of oxidative DNA damage in the causation of cancer and its prevention by antioxidants. They should also help in studying the relationship between oncogenes such as c-Myc and DNA damage...
  13. pmc c-Myc is required for the CHREBP-dependent activation of glucose-responsive genes
    Pili Zhang
    Department of Medicine, Division of Endocrinology and Metabolism, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA
    Mol Endocrinol 24:1274-86. 2010
    ..The activation and recruitment of ChREBP to several glucose-responsive genes were blocked by 1RH, indicating a general necessity for c-Myc in this process...
  14. pmc Widespread genomic instability mediated by a pathway involving glycoprotein Ib alpha and Aurora B kinase
    Youjun Li
    Section of Hematology Oncology, Children s Hospital of Pittsburgh of the University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15201, USA
    J Biol Chem 285:13183-92. 2010
    ..Suppression of Aurora B via GpIb alpha provides a unifying and mechanistic explanation for several types of Myc-mediated GI...
  15. pmc Regulation of reactive oxygen species homeostasis by peroxiredoxins and c-Myc
    J Anthony Graves
    Department of Pediatrics, Division of Hematology Oncology, Children s Hospital of Pittsburgh, and University of Pittsburgh Medical Center, Department of Microbiology and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA
    J Biol Chem 284:6520-9. 2009
    ....
  16. pmc Breast cancer stem cell-like cells are more sensitive to ionizing radiation than non-stem cells: role of ATM
    Seog Young Kim
    Department of Surgery, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America
    PLoS ONE 7:e50423. 2012
    ..These results suggest that low DNA repair capacity is responsible for the high radiosensitivity of these CSC-like cells...
  17. pmc Phenotypic screening reveals topoisomerase I as a breast cancer stem cell therapeutic target
    Fang Zhang
    Section of Hematology Oncology, Children s Hospital of Pittsburgh of UPMC, The University of Pittsburgh, Pittsburgh, Pennsylvania, USA
    Oncotarget 3:998-1010. 2012
    ..These results illustrate the substantial power of this CSC phenotypic screening platform and promote Topo I as a potential molecular therapeutic target for therapies aimed at expunging CSCs...
  18. pmc Point mutations in c-Myc uncouple neoplastic transformation from multiple other phenotypes in rat fibroblasts
    J Anthony Graves
    Division of Hematology Oncology, Department of Pediatrics, Children s Hospital of Pittsburgh of the University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, United States of America
    PLoS ONE 5:e13717. 2010
    ....
  19. pmc The negative c-Myc target onzin affects proliferation and apoptosis via its obligate interaction with phospholipid scramblase 1
    Youjun Li
    Section of Hematology Oncology, Children s Hospital of Pittsburgh, Room 8124, Rangos Research Center, 3460 Fifth Ave, Pittsburgh, PA 15213, USA
    Mol Cell Biol 26:3401-13. 2006
    ..They further suggest a contiguous link between the earliest events mediated by c-Myc and the latest ones, which culminate at the cell surface and lead to phospholipid reshuffling and cell death...
  20. pmc In vivo evolution of tumor-derived endothelial cells
    Terence F McGuire
    Division of Hematology Oncology, Department of Pediatrics, Children s Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania, United States of America
    PLoS ONE 7:e37138. 2012
    ..Consequently such cells might be capable of escaping anti-angiogenic cancer therapies by generating resistant populations...
  21. pmc c-Myc-mediated genomic instability proceeds via a megakaryocytic endomitosis pathway involving Gp1balpha
    Youjun Li
    Children s Hospital of Pittsburgh, Department of Molecular Genetics and Biochemistry, University of Pittsburgh Medical Center, and University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA 15213, USA
    Proc Natl Acad Sci U S A 104:3490-5. 2007
    ....
  22. pmc Mitochondrial structure, function and dynamics are temporally controlled by c-Myc
    J Anthony Graves
    Division of Hematology Oncology, Department of Pediatrics, Children s Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania, United States of America
    PLoS ONE 7:e37699. 2012
    ..The ETC defects that persist following Myc restoration may represent metabolic adaptations, as mitochondrial function is re-directed away from producing ATP to providing a source of metabolic precursors demanded by the transformed cell...
  23. pmc Abnormal lipid processing but normal long-term repopulation potential of myc-/- hepatocytes
    Lia R Edmunds
    Division of Hematology Oncology, Children s Hospital of Pittsburgh of the University of Pittsburgh Medical Center, Pittsburgh, PA, USA
    Oncotarget 7:30379-95. 2016
    ..myc-/- livers resemble those encountered in non-alcoholic fatty liver disease and, under sustained proliferative stress, gradually acquire the features of non-alcoholic steatohepatitis. ..
  24. ncbi request reprint Dual role for SUMO E2 conjugase Ubc9 in modulating the transforming and growth-promoting properties of the HMGA1b architectural transcription factor
    Youjun Li
    Section of Hematology Oncology, Children s Hospital of Pittsburgh, The Department of Molecular Genetics and Biochemistry, The University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15213, USA
    J Biol Chem 282:13363-71. 2007
    ..These findings are consistent with the idea that Ubc9 can act as both a positive and negative regulator of proliferation and transformation via its non-SUMO-dependent interaction with HMGA1 proteins...
  25. pmc Permanently blocked stem cells derived from breast cancer cell lines
    Gangadharan B Sajithlal
    Section of Hematology Oncology, Children s Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA
    Stem Cells 28:1008-18. 2010
    ....
  26. pmc Direct inhibition of c-Myc-Max heterodimers by celastrol and celastrol-inspired triterpenoids
    Huabo Wang
    Section of Hematology Oncology, Children s Hospital of Pittsburgh of UPMC, The University of Pittsburgh Medical Center, Pittsburgh, PA, USA
    Oncotarget 6:32380-95. 2015
    ..This, together with their low in vivo toxicity, provides a strong rationale for pursuing the development of additional Myc-specific triterpenoid derivatives. ..
  27. doi request reprint Endothelial-like cells derived directly from human tumor xenografts
    Gangadharan B Sajithlal
    Section of Hematology Oncology, Children s Hospital of Pittsburgh, Pittsburgh, PA 15201, USA
    Int J Cancer 127:2268-78. 2010
    ..These findings could have significant implications for therapies that target tumor angiogenesis...
  28. ncbi request reprint C-Myc-independent restoration of multiple phenotypes by two C-Myc target genes with overlapping functions
    Krisiti Rothermund
    Section of Hematology Oncology, Children s Hospital of Pittsburgh
    Cancer Res 65:2097-107. 2005
    ..The approach described here should permit the identification of other target genes capable of further c-Myc-independent complementation...
  29. pmc Efficacy, pharmacokinetics, tisssue distribution, and metabolism of the Myc-Max disruptor, 10058-F4 [Z,E]-5-[4-ethylbenzylidine]-2-thioxothiazolidin-4-one, in mice
    Jianxia Guo
    Hillman Cancer Center, The University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213, USA
    Cancer Chemother Pharmacol 63:615-25. 2009
    ..In vitro studies indicate the thioxothiazolidinone, 10058-F4, inhibits c-Myc/Max dimerization. In this study, we report the efficacy, pharmacokinetics and metabolism of this novel protein-protein disruptor in mice...
  30. ncbi request reprint Improved low molecular weight Myc-Max inhibitors
    Huabo Wang
    Section of Hematology Oncology, Children s Hospital of Pittsburgh, Pittsburgh, PA 15213, USA
    Mol Cancer Ther 6:2399-408. 2007
    ..They further show that the compounds specifically target c-Myc, which exists in a dynamic and relatively unstructured state with only partial and transient alpha-helical content...
  31. ncbi request reprint Low molecular weight inhibitors of Myc-Max interaction and function
    Xiaoying Yin
    Section of Hematology Oncology, Children s Hospital of Pittsburgh, Pittsburgh, PA 15213, USA
    Oncogene 22:6151-9. 2003
    ..More specifically, they provide a means by which structural analogs, based upon these first-generation Myc-Max inhibitors, can be developed to enhance antitumor efficacy...
  32. pmc Rapid in vitro derivation of endothelium directly from human cancer cells
    Jennifer D Elster
    Division of Hematology Oncology, Department of Pediatrics, Children s Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania, United States of America
    PLoS ONE 8:e77675. 2013
    ..These studies provide a suitable means by which to identify and perhaps modify the earliest steps in TDEC generation. ..
  33. pmc Disruption of Myc-Max heterodimerization with improved cell-penetrating analogs of the small molecule 10074-G5
    Huabo Wang
    Section of Hematology Oncology, Children s Hospital of Pittsburgh of UPMC, Pittsburgh, PA, USA
    Oncotarget 4:936-47. 2013
    ..Analogs of JY-3-094 appear to represent promising small molecule Myc inhibitors that warrant further optimization. ..
  34. ncbi request reprint The CCL6 chemokine is differentially regulated by c-Myc and L-Myc, and promotes tumorigenesis and metastasis
    Fenghua Yi
    Department of Pediatrics, Children s Hospital of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA
    Cancer Res 63:2923-32. 2003
    ..The chemokine may alter tumor behavior by relieving its growth factor dependency and by promoting invasiveness as a result of local tissue apoptosis...
  35. ncbi request reprint A functional hierarchy for c-Myc target genes? Lessons from MT-MC1
    Debra E Cohen
    Section of Hematology Oncology, Children s Hospital of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA
    Cell Cycle 5:392-3. 2006
    ..This is supported by the finding that nearly half of MT-MC1-regulated genes have been previously implicated in cancer...
  36. pmc c-Myc and AMPK Control Cellular Energy Levels by Cooperatively Regulating Mitochondrial Structure and Function
    Lia R Edmunds
    Section of Hematology Oncology, Children s Hospital of Pittsburgh of UPMC, Pittsburgh, PA, United States of America The University of Pittsburgh School of Medicine, Pittsburgh, PA, United States of America
    PLoS ONE 10:e0134049. 2015
    ..Thus, Myc and AMPK are highly co-dependent and appear to engage in significant cross-talk across numerous pathways which support metabolic and ATP-generating functions. ..
  37. pmc Structurally diverse c-Myc inhibitors share a common mechanism of action involving ATP depletion
    Huabo Wang
    Division of Hematology Oncology, Children s Hospital of Pittsburgh of University of Pittsburgh Medical Center, Pittsburgh, PA, USA
    Oncotarget 6:15857-70. 2015
    ..Thus, all Myc inhibitors promote a global energy collapse that appears to underlie many of their phenotypic consequences...
  38. ncbi request reprint c-Myc as a therapeutic target in cancer
    Edward V Prochownik
    Section of Hematology Oncology, Children s Hospital of Pittsburgh, Rangos Research Center, Room 2100, 3460 Fifth Avenue, Pittsburgh, PA 15213, USA
    Expert Rev Anticancer Ther 4:289-302. 2004
    ....
  39. ncbi request reprint Myc target in myeloid cells-1, a novel c-Myc target, recapitulates multiple c-Myc phenotypes
    Xiaoying Yin
    Section of Hematology Oncology, Children s Hospital of Pittsburgh, The Department of Molecular Genetics and Biochemistry, The University of Pittsburgh, and the University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania 15213, USA
    J Biol Chem 277:19998-20010. 2002
    ..Finally, MT-MC1 regulates the expression of several other c-Myc target genes. MT-MC1 represents a proximal and direct c-Myc target that recapitulates many of the properties typically associated with Myc oncoprotein overexpression...
  40. ncbi request reprint Mutation of the MXI1 gene in prostate cancer
    L R Eagle
    Department of Pediatrics, Children s Hospital of Pittsburgh, Pennsylvania 15213, USA
    Nat Genet 9:249-55. 1995
    ..MXI1 thus displays allelic loss and mutation in some cases of prostate cancer that may contribute to the pathogenesis or neoplastic evolution of this common malignancy...
  41. ncbi request reprint Mmip1: a novel leucine zipper protein that reverses the suppressive effects of Mad family members on c-myc
    K Gupta
    Section of Hematology Oncology, Childrens Hospital of Pittsburgh, Pennsylvania 15213, USA
    Oncogene 16:1149-59. 1998
    ..By interfering with the dimerization between Max and Mad family member proteins, Mmip1 can indirectly up-regulate the transcriptional activity of c-myc and suppress the antiproliferative actions of Mad proteins...
  42. ncbi request reprint Commonly occurring loss and mutation of the MXI1 gene in prostate cancer
    E V Prochownik
    Section of Hematology Oncology, Children s Hospital of Pittsburgh, Pennsylvania 15213, USA
    Genes Chromosomes Cancer 22:295-304. 1998
    ..Five of the mutant proteins were unable to bind DNA in association with MAX. We conclude that MXI1 gene loss in prostate cancer is common and most frequently involves a cytogenetically undetectable deletion...
  43. ncbi request reprint Mmip-2/Rnf-17 enhances c-Myc function and regulates some target genes in common with glucocorticoid hormones
    X Y Yin
    Section of Hematology/Oncology, Children's Hospital of Pittsburgh, Pennsylvania, PA 15213, USA
    Oncogene 20:2908-17. 2001
    ..Our results also identify a previously unrecognized overlap between genes regulated by c-Myc- and GCs and provide a potential molecular basis for their regulation of common cellular functions...
  44. ncbi request reprint Dynamic in vivo interactions among Myc network members
    X Yin
    Section of Hematology Oncology, Department of Pediatrics, Children s Hospital of Pittsburgh, Pittsburgh, Pennsylvania, PA 15213, USA
    Oncogene 20:4650-64. 2001
    ..These findings suggest novel means by which Myc network members promote transcriptional activation or repression...