Abrogation by c-myc of Gl phase arrest induced by RB protein but not by p53

Abstract

INACTIVATING mutations of the retinoblastoma gene (RB) are found in a wide variety of tumour cells¹. 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^2–4. As activation of c-myc expression promotes cell proliferation and blocks differentiation, it may positively regulate cell growth^5–9. The c-myc protein is localized in the nucleus and can physically associate with RB protein in vitro¹⁰, hence c-myc may functionally antagonize RB function. Microinjection of Rb in Gl phase reversibly arrests cell-cycle progression¹¹. 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.