Phosphorylation of the C terminus of Fos protein is required for transcriptional transrepression of the c-fos promoter.
Proto-oncogene fos encodes a nuclear phosphoprotein of 380 amino acids that can modulate the transcription of other genes either by transactivation or by transrepression. The v-Fos protein (381 amino acids) shares the first 332 amino acids with the c-Fos protein (with five single amino-acid changes), but differs at the C terminus. We have previously reported that the c-Fos protein undergoes more extensive post-translational modification than v-Fos (refs 9, 10). The major modification of the c-Fos protein involves serine phosphoesterification of sites in the extreme C terminus. We therefore argued that modification of the C-terminal region of the c-Fos protein may be involved in its ability to transrepress transcription without compromising its ability to transactivate other genes. Here we show that mutant c-Fos protein which is hypophosphorylated at its C terminus is unable to repress transcription of the c-fos promoter following induction with serum or tetraphorbol acetate. The C-terminal phosphorylation-deficient mutant is, however, fully competent to activate transcription of promoters containing a phorbol response element. The requirement for phosphorylation can be offset by the introduction of a net negative charge in the C terminus of the Fos protein.
Ofir
R
R
Molecular Biology and Virology Laboratory, Salk Institute, San Diego, California 92138.
Dwarki
V J
VJ
Rashid
D
D
Verma
I M
IM
D000595:Amino Acid Sequence; D001483:Base Sequence; D002460:Cell Line; D007163:Immunosorbent Techniques; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010766:Phosphorylation; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos; D013489:Suppression, Genetic; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic; D014162:Transfection
D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D013755:Tetradecanoylphorbol Acetate