chapter  8
18 Pages

Transcriptional Regulation of the Human c-fos Proto-Oncogene

WithAlfred Nordheim, Ralf Janknecht, Robert A. Hipskind

The c-fos proto-oncogene is rapidly induced to maximal transcriptional activity when quiescent cells are stimulated to grow by the addition of serum or individual growth factors. The crucial role fulfilled by serum response element binding factor (SRF) for serum response element (SRE)-dependent c-fos induction has been amply demonstrated by mutational analysis and by microinjection of anti-SRF antibodies. The binary SRE-SRF complex interacts with another binding activity termed ternary complex factor (TCF), thereby generating a stable ternary complex. TCFs have been shown to contribute to the efficiency of the serum response. The protein components of the ternary complex, namely TCFs and possibly SRF itself, appear to be direct substrates for signaling-dependent phosphorylation and dephosphorylation. The proteins bound to the SRE, namely SRF and TCF, represent the likely targets of the incoming, SRE-directed signals. Several reports indicate that Fos transrepression is effected through the SRE.