6th EditionDavid L Nelson, Michael M. Cox616 explanations
1st EditionJoseph S. Levine, Kenneth R. Miller1,773 explanations
5th EditionCharlotte W. Pratt, Donald Voet, Judith G. Voet980 explanations
10th EditionCain, Campbell, Minorsky, Reece, Urry, Wasserman1,706 explanations
BIOLOGYMyc is a transcription factor that regulates cell proliferation; mutations in the myc gene contribute to many cases of the cancer Burkitt lymphoma. Initial experiments on Myc were puzzling. The Myc protein contains both a leucine zipper dimerization domain and a specialized type of helix-loop-helix DNA-binding domain called a bHLH motif, but purified Myc can neither homodimerize nor bind to DNA efficiently. Discovery of the Max and Mad Proteins helped resolve this dilemma, Like Myc, Max and Mad each contain a bHLH motif and a leucine zipper, but neither Max nor Mad homodimerize readily form and bind DNA with high affinity. However, Myc-Max and Mad-Max heterodimers do readily form and bind DNA; in fact, they bind the same sites on the enhancers of the same target genes. Myc contains an activation domain, while Mad contains a repression domain and Max contains neither. The max gene is expressed in all cells at all times. In contrast, mad is expressed in resting cells (in the
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phase of the cell cycle), while myc is not transcribed in resting cells but starts to be expressed when cells are about to divide (at the transition from
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0 to S phase). Mad and Myc proteins are unstable relative to Max protein; when expression of mad or myc ceases, Mad or Myc proteins soon disappear. a. Do you think target genes with enhancers containing binding sites for Myc-Max encode proteins that would arrest the cell cycle or that would drive the cell cycle forward? What about genes with enhancers containing binding sites for Mad-Max? Explain your answers. b. Draw diagrams to show the control region for a target gene, the proteins binding to the enhancer and whether or not transcription is taking place in (i) resting cells and (ii) cells that are about to divide. c. Provide a concise summary of how these three proteins can regulate cell proliferation. d. Would cancer-causing mutations in myc be loss-of-function or gain-of-function mutations?
