The c-myc oncoprotein forms a specific complex with the product of the retinoblastoma gene

Abstract

Myc proteins are involved in the regulation of cell proliferation and differentiation. Deregulated expression of myc family genes has been implicated in the genesis of a variety of cancers. Myc proteins share significant sequence homology in the carboxyl terminus with a number of cellular transcription factors. These basic domain-helix-loophelix and leucine zipper motifs have been shown to be involved in protein dimerization and DNA binding. Indeed, evidence now exists to indicate that the c-myc, N-myc, and L-myc proteins can form a heterodimer with a cellular protein, named MAX, and that the myc-MAX heterodimer can bind to DNA in a sequence-specific fashion. In addition, myc proteins have several amino-terminal regions that are highly conserved between myc family members. These regions of homology are not found in other cellular proteins but are essential for transformation. On the basis of these observations, it would appear likely that myc proteins function in cell growth by regulating the activity of a number of cellular genes whose products control cell proliferation. Several groups have identified cellular genes that are subject to regulation by myc proteins. However, none of these genes is likely to be directly involved in the control of cell cycle progression. We show here that amino-terminal sequences in the c-myc protein mediate specific binding to the product of the retinoblastoma gene, pRB. We propose a model in which activity of the c-myc protein is modulated through binding to the retinoblastoma gene product.