Amino-terminal domains of c-myc and N-myc proteins mediate binding to the retinoblastoma gene product.
The proteins encoded by the myc gene family are involved in the control of cell proliferation and differentiation, and aberrant expression of myc proteins has been implicated in the genesis of a variety of neoplasms. In the carboxyl terminus, myc proteins have two domains that encode a basic domain/helix-loop-helix and a leucine zipper motif, respectively. These motifs are involved both in DNA binding and in protein dimerization. In addition, myc protein family members share several regions of highly conserved amino acids in their amino termini that are essential for transformation. We report here that an N-terminal domain present in both the c-myc and N-myc proteins mediates binding to the retinoblastoma gene product, pRb. We show that the human papilloma virus E7 protein competes with c-myc for binding to pRb, indicating that these proteins share overlapping binding sites on pRb. Furthermore, a mutant Rb protein from a human tumour cell line that carried a 35-amino-acid deletion in its C terminus failed to bind to c-myc. Our results suggest that c-myc and pRb cooperate through direct binding to control cell proliferation.
Rustgi
A K
AK
Division of Molecular Genetics, Massachusetts General Hospital, Charlestown.
Dyson
N
N
Bernards
R
R
D000595:Amino Acid Sequence; D015153:Blotting, Western; D002455:Cell Division; D016161:Genes, Retinoblastoma; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D008969:Molecular Sequence Data; D011485:Protein Binding; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism*
D016271:Proto-Oncogene Proteins c-myc; D011993:Recombinant Fusion Proteins; D016160:Retinoblastoma Protein; D005982:Glutathione Transferase