Phosphorylation of the C terminus of Fos protein is required for transcriptional transrepression of the c-fos promoter

Rivka Ofir, V. J. Dwarki, Dana Rashid, Inder M. Verma

Research output: Contribution to journalArticlepeer-review

137 Scopus citations

Abstract

PROTO-ONCOGENE fos encodes a nuclear phosphoprotein of 380 amino acids that can modulate the transcription of other genes either by transactivation or by transrepression1-7. 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 terminus8. 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 terminus10. 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 hypophosphorv lated 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.

Original languageEnglish
Pages (from-to)80-82
Number of pages3
JournalNature
Volume348
Issue number6296
DOIs
StatePublished - 1 Jan 1990
Externally publishedYes

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