Properties of the c-Myc Protein

Biology is full of surprises, and the regulation of c-myc readily illustrates this point. The regulation of c-myc expression is an intricate network of commands that controls transcriptional initiation, elongation as well as mRNA stability. In addition to this hierarchy of controls, production of the c-Myc polypeptides is also regulated. The predicted size of the c-myc encoded polypeptide initiated at the canonical AUG translational start site is 439 amino acids.1 The corresponding ATG is located at the 5' end of exon 2 (Fig. 4.1). Although the predicted molecular mass is 49.5 kDa, the observed size in sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) is about 62 kDa, which is largely due to the amino acid composition rather than to posttranslational modification.2–4 Hence this protein is termed p62Myc. From the same c-myc mRNAs, an alternative form of c-Myc polypeptide is translationally initiated at a CUG, 14 codons upstream from the canonical AUG (Fig. 6.1).5 This alternative form is termed p64Myc. These two forms of c-Myc appear as a doublet of polypeptides on SDS-PAGE.