Abrogation by c-myc of G1 phase arrest induced by RB protein but not by p53.
Inactivating mutations of the retinoblastoma gene (RB) are found in a wide variety of tumour cells. Replacement of wild-type RB can suppress the tumorigenicity of some of these cells, suggesting that the RB protein (Rb) may negatively regulate cell growth. As activation of c-myc expression promotes cell proliferation and blocks differentiation, it may positively regulate cell growth. The c-myc protein is localized in the nucleus and can physically associate with RB protein in vitro, hence c-myc may functionally antagonize RB function. Microinjection of Rb in G1 phase reversibly arrests cell-cycle progression. Here we co-inject RB protein with c-myc, EJ-ras, c-fos or c-jun protein. Co-injection of c-myc, but not EJ-ras, c-fos or c-jun, inhibits the ability of Rb to arrest the cell cycle. The c-myc does not inhibit the activity of another tumour supressor, p53 (ref. 12). Thus, c-myc and RB specifically antagonize one another in the cell.
Goodrich
D W
DW
Center for Molecular Medicine, University of Texas Health Science Center, San Antonio 78245.
Lee
W H
WH
D000818:Animals; D003513:Cycloheximide / Q000494:pharmacology; D016193:G1 Phase / Q000502:physiology*; D006801:Humans; D008845:Microinjections; D016760:Proto-Oncogene Proteins c-fos / Q000502:physiology; D016755:Proto-Oncogene Proteins c-jun / Q000494:pharmacology / Q000502:physiology; D016271:Proto-Oncogene Proteins c-myc / Q000502:physiology*; D016160:Retinoblastoma Protein / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D016271:Proto-Oncogene Proteins c-myc; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; D003513:Cycloheximide