1. The Myc Transcription Factor
By: Michael Reisfeld

2. MYC Was Originally cloned From a transforming Virus
Chicken head tumor
Lanes a-e represent different lengths of human DNA. pMC5 is 5’ end of myc sequence, pMC3 is 3’ end of myc sequence, pMC0 contains entire myc sequence

3. Myc is a Transcription Factor Which Dimerizes With a Leucine Zipper and binds to DNA Via a Helix-Loop-Helix

4. Myc is part of pathway that promotes Cell Proliferation

5. Myc Targets a Huge Array of Genes to Perform This Function
Northern blot showing rna expression increasing when myc-ER fusion protein is combined with estrogen analog 4-hydroxytamoxifen (4OHT); in C, p21 expression is repressed by myc
Venn diagrams show genes that were activated by myc according to what independent experiment was being done

6. Myc is a Family of Three Proteins, in Which Each Possesses a Slightly different Function
C-myc and n-myc KOs are embryonic lethal. L-myc KOs have no phenotype.
In the experiment above, c-myc and n-myc were preferentially knocked out in hematopoetic stem cells. The DKO was rapidly lethal, much more so than an individual KO of either. In neural tissue, n-myc KOs cause severe lack of brain development but c-myc KOs affect mostly growth

7. Neuroblastoma (N-myc)
Overexpression of Each Specific Myc Protein Is Responsible for Corresponding Tumor Types
Neuroblastoma (N-myc)
Burkitt’s Lymphoma (c-myc)
Small Cell Lung Cancer (L-myc)

8. c-Myc Overexpression Can Induce Tumors
human c-myc was cloned into mice at both high (HI) and low (Low) levels. Both mice lines develop aggressive prostatic cancer
mPIN: mouse prostatic intraepithelial neoplasia

9. A More Human Side…

10. Burkitt’s Lymphoma 2% of Lymphoproliferative Disorders
C-myc translocation associated with ALL cases
85% involve translocation to IGH

11. Is Myc a Viable Target for Treatment?

12. Works Cited
Bellan, C et al. “Burkitt’s lymphoma: new insights into molecular pathogenesis.” Journal of Clinical Pathology. 11 July 2002; 56:3, Coller HA, Grandori C, Tamayo P, Colbert T, Lander ES, Eisenman RN, et al. ”Expression analysis with oligonucleotide microarrays reveals that MYC regulates genes involved in growth, cell cycle, signaling, and adhesion.” Proc Natl Acad Sci USA. 2000; 97(7): Dalla-Favera R, et al. “Cloning and characterization of different human sequences related to the onc gene (v-myc) of avian myelocytomatosis virus (MC29).” Proc Natl Acad Sci U S A. 1982;79:6497–501 Ellwood-Yen, Katherine et al. “Myc-driven murine prostate cancer shares molecular features with human prostate tumors.” UClA. Hatton, Kimi S et al. “Expression and Activity of L-Myc in Normal Mouse Development.” Molecular and Cellular Biology. 1996; 16:4, Henriksson, Marie and Marina Vita. “The Myc oncoprotein as a therapeutic target for human cancer.” Seminars in Cancer Biology. 2006; 16, Laurenti, Elisa et al. “Hematopoietic Stem Cell function and Survival Depend on c-myc and N-myc activity.” Cell Stem Cell. 4 Dec 2008; 3:6, Nesbitt, Chad et al. “Myc Oncogenes and human neoplastic disease.” Oncogene. 13 May 1999; 18:19, Penn, Linda Z and Amanda R. Wasylishen. “Myc: The Beauty and the Beast.” Genes and Cancer. 26 July 2010; 1:6, Wey, Alice et al. “c- and N-myc Regulate Neural Precursor Cell Fate, Cell Cycle, and Metabolism to Direct Cerebellar Development.” Cerebellum. Dec 2010; 9:4,