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Burkitt lymphoma and myelocytomatosis proto-oncogene (MYC)

Burkitt lymphoma and myelocytomatosis proto-oncogene (MYC). Deeter Neumann. History of Burkitt Lymphoma. 1887 Sir Albert Cook Reports of mass in jaw area 1934 Smith and Elmes “round cell sarcomas” 1953 Capponi ovary lymphosarcoma in Cameroon children 1958 Dr. Burkitt

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Burkitt lymphoma and myelocytomatosis proto-oncogene (MYC)

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  1. Burkitt lymphoma and myelocytomatosis proto-oncogene (MYC) Deeter Neumann

  2. History of Burkitt Lymphoma 1887 Sir Albert Cook Reports of mass in jaw area 1934 Smith and Elmes “round cell sarcomas” 1953 Capponi ovary lymphosarcoma in Cameroon children 1958 Dr. Burkitt Specific clinical syndrome “Lymphoma belt” Denis Burkitt http://www.canceruptodate.blogspot.com/

  3. Burkitt Lymphoma B cell lymphoma Most common form of tumor found in African children 3 Subtypes Endemic Sporadic Immunodeficiency-associated “Starry Sky” histology Tumor http://commons.wikimedia.org/wiki/File:Burkitt%27s_lymphoma.jpg http://www.radiology.casereports.net/index.php/rcr/article/viewArticle/179/486

  4. MYC positioned on Chromosome 8 Located at 8q24.21 Encodes a nuclear phosphoprotein Regulates cell proliferation differentiation apoptosis http://www.genecards.org/cgi-bin/carddisp.pl?gene=Myc http://ghr.nlm.nih.gov/handbook/illustrations/apoptosismacrophage

  5. MYC’s role in Burkitt Lymphoma Chromosomal translocation disrupting immunoglobin (Ig) genes Ig locus control of MYC Constitutive MYC expressed in B-cells http://science.kukuchew.com/tag/immunoglobulin/ http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=gnd.section.148&ref=sidebar

  6. MYC Protein 454 amino acids MYC_N HLH MYC-LZ MYC_N amino-terminal HLH helix-loop-helix MYC-MAX MYC-LZ leucine zipper dimerization domain http://www.ncbi.nlm.nih.gov/homologene/31092?ordinalpos=1&itool=EntrezSystem2.PEntrez.Homologene.Homologene_ResultsPanel.Homologene_RVDocSum

  7. Gene Ontology http://www.ebi.ac.uk/QuickGO/GProtein?ac=P01106

  8. MYC tag MYC is a small protein Proteins lacking specific Antibodies (Ab) Create recombinant protein Identify the Protein using anti-MYC Abs https://www.cellsignal.com/products/images/2276_fig3.jpg

  9. Homo sapien Rattus norvegicus Mus musculus Drosophila melanogaster Pan troglodytes Danio rerio Canis lupus familiaris Bos taurus MYC Phylogeny mRNA sequences were used to create phylogram using clustalW https://www.dpchallenge.com/image.php?IMAGE_ID=523504

  10. DNA Motifs 7 DNA motifs found Stimulating Protein 1 (Sp1) Interest in Sp1 Protein found in humans DNA-binding protein Regulates “prosurvival proteins” and “prodeath proteins” http://motif.genome.jp/

  11. Human Protein Network MAX SMAD3 MM-1 (PFDN5) http://string.embl.de

  12. Mouse Protein Network MM-1 http://string.embl.de

  13. Fly Protein Network http://string.embl.de

  14. Fly and Mouse Models Human protein Mouse protein Fly protein Rat protein http://www.ncbi.nlm.nih.gov/homologene/31092?ordinalpos=1&itool=EntrezSystem2.PEntrez.Homologene.Homologene_ResultsPanel.Homologene_RVDocSum

  15. Modeling MYC in Fly Investigated roles of drosophilaMyc (dMyc) and Mnt Null dMyc- effect on organismal and cellular growth Created dm4 null mutant and dm4dmnt1 flies

  16. dm4 vs. dm4dmnt1

  17. ribosome dMyc vs dMnt dMnt major regulatory role at dMyc target genes dMnt function limits cell growth Loss of dMyc affects protein synthesis http://media.photobucket.com/image/ribosome/bmahfood/Blog%20Photos/ribosome1.jpg

  18. Knock-in Mice Myctm1Lbox Allele knock-in IgH 3’ enhancer upstream of Myc locus Created heterozygote and homozygote http://www.jimmunol.org/cgi/content/full/179/9/6033#F1

  19. WT vs. IgH-3’E-myc mouse WT spleen IgH-3’E-myc spleen Lymph node Spleen IgH-3’E-myc spleen Lymphoma in lung Lymphoma in kidney http://www.jbc.org/cgi/content/full/280/13/12766

  20. Mouse Model for Burkitt Lymphoma Homo Het B cell http://www.biooncology.com/bioonc/research/b-cellbiology/index.m http://www.informatics.jax.org/javawi2/servlet/WIFetch?page=alleleDetail&key=39047

  21. Future Directions Understand the cause of translocation Gene therapy with MM-1 or Smad3 to supress tumorigenesis? Microarrays to detect specific interactions of genes in both Burkitt patient and normal individual Target other bHLH rescue proteins Cell cycle progression in normal and Burkitt cells Utilize rat as model organism! ??? https://eapbiofield.wikispaces.com/Chapter+12+Kendall

  22. References Boxer, LM., Wang, j. (2005). Regulatory elements in the immunoglobin heavy chain gene 3’-enhancers induce c-myc deregulation and lymphomagenesis in murine B cells. Journal of Biological Chemistry. 280(13). Retrieved from: http://www.jbc.org/cgi/content/full/280/13/12766 Burkitt, D. (1962). A Lymphoma Syndrome in African Children. Annals of the Royal College of Surgeons of England. 30(4):211-219. Retrieved from: http://www.pubmedcentral.nih.gov/pagerender.fcgi?artid=2414150&pageindex=9#page Feng, X., Liang, Y., and Liang, M.(2002).Direct Interaction of c-Myc with Smad2 and Smad3 to Inhibit TGF-β-Mediated Induction of the CDK Inhibitor p15Ink4B. Molecular Cell. 9(1):133-143. Retrieved from: http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6WSR-4C5RFFB-J&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=5ed8f5bd595b7103fdbe1b0aa055b850 Hagio, Y., Kimura, Y., and Taira, T. (2006) Distinct localizations and repression activities of MM-1 isoforms toward c-Myc. Journal of Biological Chemistry. 97(1):145-55. Pierce, SB., Yost, C., and Andersen, S. (2008). Drosophila growth and development in absence of dMyc and dMnt. Developmental Biology. 315(2):303-316. Retrieved from: http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6WDG-4RFJ4N1-1&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=9b9a25effa5156ae728c4d67c7b2e772 Thorley-Lawson, DA., Allday, MJ. (2008). The Curious case of the tumor virus: 50 years of Burkitt Lymphoma. Nature Reviews. 6:913-922 Ryu, H., Lee, J., Zaman, K., Kubulis, J., Ferrante, R. J., Ross, B. D., Neve, R., Ratan, R. R. (2003). Sp1 and Sp3 are Oxidative Stress-Inducible, Antideath Transcriptional Factors in Cortical Neurons. The Journal of Neuroscience. 23(9):3597. Retrieved from: http://www.jneurosci.org/cgi/content/full/23/9/3597?maxtoshow=&HITS=&hits=&RESULTFORMAT=1&andorexacttitle=and&fulltext=Sp1&andorexactfulltext=and&searchid=1&FIRSTINDEX=0&sortspec=relevance&resourcetype=HWCIT

  23. Questions?

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