The basic region/helix-loop-helix/leucine zipper domain of Myc proto-oncoproteins: Function and regulation

A large body of evidence has been accumulated that demonstrates dominant ef fects of Myc proto-oncoproteins on different aspects of cellular growth, My c is one of the few proteins that is sufficient to drive resting cells into the cell cycle and promote DNA synthesis. In line with this finding is tha t the constitutive expression of Myc in cells blocks their differentiation. These growth stimulating properties are most likely responsible for Myc's ability to initiate and promote tumor formation, Interestingly Myc can also sensitize cells to apoptosis, suggesting that this protein is part of a li fe-and-death switch. Molecularly Myc functions as a transcriptional regulat or that needs to heterodimerize with Max to exert the biological activities described above and to regulate gene transcription, Myc and Max are just t wo members of a growing family of proteins referred to as the Myc/Max/Mad n etwork. A hallmark of these proteins is that they possess a C-terminal basi c region/helix-loophelix/leucine zipper domain (bHLHZip). The bHLHZip domai n specifies dimerization within the network and determines sequence specifi c DNA binding. Importantly this domain together with the N-terminal transac tivation domain is essential for Myc biology. Here we have summarized the s tructural, functional, and regulatory aspects of the bHLHZip domain of Myc proteins.