The Myc Transcription Factor By: Michael Reisfeld

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

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

Myc is part of pathway that promotes Cell Proliferation

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

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

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)

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

A More Human Side…

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

Is Myc a Viable Target for Treatment?

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