Goodrich D W, Lee W H
Center for Molecular Medicine, University of Texas Health Science Center, San Antonio 78245.
Nature. 1992 Nov 12;360(6400):177-9. doi: 10.1038/360177a0.
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.
在多种肿瘤细胞中都发现了视网膜母细胞瘤基因（RB）的失活突变。野生型RB的替代可抑制其中一些细胞的致瘤性，这表明RB蛋白（Rb）可能对细胞生长起负调控作用。由于c-myc表达的激活促进细胞增殖并阻断分化，它可能对细胞生长起正调控作用。c-myc蛋白定位于细胞核，并且在体外可与RB蛋白发生物理结合，因此c-myc可能在功能上拮抗RB的功能。在G1期显微注射Rb可使细胞周期进程可逆性停滞。在此，我们将RB蛋白与c-myc、EJ-ras、c-fos或c-jun蛋白共同注射。共同注射c-myc而非EJ-ras、c-fos或c-jun可抑制Rb使细胞周期停滞的能力。c-myc并不抑制另一种肿瘤抑制因子p53的活性（参考文献12）。因此，c-myc和RB在细胞中特异性地相互拮抗。
