Inducible cAMP Early Repressor (ICER) and Brain Functions

Abstract

The inducible cAMP early repressor (ICER) is an endogenous repressor of cAMP-responsive element (CRE)-mediated gene transcription and belongs to the CRE-binding protein (CREB)/CRE modulator (CREM)/activating transcription factor 1 (ATF-1) gene family. ICER plays an important role in regulating the neuroendocrine system and the circadian rhythm. Other aspects of ICER function have recently attracted heightened attention. Being a natural inducible CREB antagonist, and more broadly, an inducible repressor of CRE-mediated gene transcription, ICER regulates long-lasting plastic changes that occur in the brain in response to incoming stimulation. This review will bring together data on ICER and its functions in the brain, with a special emphasis on recent findings highlighting the involvement of ICER in the regulation of long-term plasticity underlying learning and memory.

Activation of Intracellular Metabotropic Glutamate Receptor 5 in Striatal Neurons Leads to Up-regulation of Genes Associated with Sustained Synaptic Transmission Including Arc/Arg3.1 Protein

“…As described, Arc is critical for various forms of LTP and LTD (10). Crem is also involved in the regulation of long term plasticity underlying learning and memory (39). Finally, Nr4a1 (Nurr77), JunB (supplemental Table S1), c-Fos, and Egr1 (1) have all been linked to synaptic remodeling and, in some cases, learning and memory (25,40).…”

“…Other genes such as Snf1lk (SIK1) repress CREB-dependent transcriptional activity both in the nucleus and in the cytoplasm (38). Indeed, Crem acts as a natural antagonist of cAMP-response element (CRE)-mediated gene transcription (39). Thus, one initial outcome of intracellular mGluR5 activation is to damp down CREB signaling and promote SRF-mediated IEGs.…”

cAMP Response Element-Binding Protein Is a Primary Hub of Activity-Driven Neuronal Gene Expression

“…4 B). Other relevant examples are Crem, whose analysis at the probeset level demonstrated the specific activation by caCREB and fsk of the internal CRE-bearing promoter that drives the expression of the inducible cAMP early repressor (ICER) protein (Borlikova and Endo, 2009) (Fig. 4C) and Homer1, whose short isoform Homer1a that functions as an inducible dominantnegative form (Brakeman et al, 1997), is specifically regulated by bic and more modestly by caCREB and fsk (Fig.…”

Inducible cAMP Early Repressor Regulates the Period 1 Gene of the Hepatic and Adrenal Clocks

“…It is believed that it has an important role in suppressing bursts of different neuronal signals that could be damaging for the nervous system (42). ICER acts as a kind of noise filter that maintains the normal nervous activity.…”