Inducibility and negative autoregulation of CREM: An alternative promoter directs the expression of ICER, an early response repressor

Carlos A. Molina, Nicholas S. Foulkes, Enzo Lalli, Paolo Sassone-Corsi

Research output: Contribution to journalArticle

503 Scopus citations

Abstract

cAMP-responsive element modulator (CREM) expression is tissue specific and developmentally regulated. Here we report that CREM is unique within the family of cAMP-responsive promoter element (CRE)-binding factors since it is inducible by activation of the cAMP signaling pathway. The kinetic of expression is characteristic of an early response gene. The induction is transient and cell specific, does not involve increased transcript stability, and does not require protein synthesis. Significantly, the subsequent decline in CREM expression requires de novo protein synthesis. The induced transcript encodes a novel repressor, inducible cAMP early repressor (ICER), and is generated from an alternative intronic promoter. A cluster of four CREs in this promoter directs cAMP inducibility. ICER binds to these elements and thereby represses the activity of its own promoter, thus constituting a negative autoregulatory loop.

Original languageEnglish
Pages (from-to)875-886
Number of pages12
JournalCell
Volume75
Issue number5
DOIs
StatePublished - 3 Dec 1993

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