TY - JOUR
T1 - Inducibility and negative autoregulation of CREM
T2 - An alternative promoter directs the expression of ICER, an early response repressor
AU - Molina, Carlos A.
AU - Foulkes, Nicholas S.
AU - Lalli, Enzo
AU - Sassone-Corsi, Paolo
PY - 1993/12/3
Y1 - 1993/12/3
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0027741257&partnerID=8YFLogxK
U2 - 10.1016/0092-8674(93)90532-U
DO - 10.1016/0092-8674(93)90532-U
M3 - Article
C2 - 8252624
AN - SCOPUS:0027741257
SN - 0092-8674
VL - 75
SP - 875
EP - 886
JO - Cell
JF - Cell
IS - 5
ER -