Nuclear Oncoproteins Determine the Genetic Program in Response to External Stimuli (original) (raw)

1. A. Schönthal,
2. S. Gebel,
3. B. Stein,
4. H. Ponta,
5. H.J. Rahmsdorf, and
6. P. Herrlich
7. Kernforschungzentrum Karlsruhe, Institut für Genetik und Toxikologie and Universität Karlsruhe, Institut für Genetik, D-7500 Karlsruhe 1, Federal Republic of Germany

Excerpt

The genetic response of mammalian cells to changes in extracellular conditions requires preexisting signal-receiving structures, transfer of the message from these to the nucleus, and a recognition mechanism of the subset of genes to be activated or repressed. For instance, a steroid hormone finds a preexisting high-affinity receptor protein within the cell (for review, see Evans 1988) that possesses the ability to select genes by recognizing a defined _cis_-acting sequence element (Chandler et al. 1983; Hynes et al. 1983; Majors and Varmus 1983; Karin et al. 1984; Klein-Hitpass et al. 1986). Only genes carrying this sequence element will become activated, and the hormone-dependent response is limited to cells in which the receptor protein is present. In studying the mechanism of phorbol-ester-, UV-radiation-, and growth-factor-induced gene expression, we have come across another type of signal transfer from outside the cells to the nucleus. Several preexisting protein macromolecules participate in receiving and...