Disease relevance of Crem

• Overexpression of CREM-17X in intact islets via adenovirus infection decreased islet insulin mRNA levels and insulin content and resulted in a significant decrease in glucose- or KCl-induced insulin secretion [1].

High impact information on Crem

• Inducibility and negative autoregulation of CREM: an alternative promoter directs the expression of ICER, an early response repressor [2].
• Transcription factor CREM (cAMP-responsive element modulator) plays a pivotal role in the nuclear response to cAMP in neuroendocrine cells [3].
• Transient transfection of the insulin-secreting beta HC9 cells with CREM-17X suppressed rat insulin promoter activity by nearly 50% [1].
• Here we show that CREM (cAMP Responsive Element Modulator) expression is induced rapidly upon prostaglandin E1 treatment of IPC-81 cells [4].
• The study shows that generation of ICER following prolonged stimulation with forskolin, or transfection of an ICER expression vector in hypothalamic cell lines expressing CRH, is associated with CREM binding to the CRH promoter and transcriptional repression [5].

Biological context of Crem

• In this study, we found that administration of all-trans retinoic acid (ATRA) or retinol to VAD rats down-regulates the testicular mRNA levels of the cAMP responsive element modulator (CREM), an essential transcription factor for spermatogenesis [6].
• Conversely, depletion of retinoids from the diet leds to an up-regulation of CREM expression in adult testes [6].
• Here we show that in Sertoli cells FSH-mediated induction of the CREM repressor isoform, ICER (inducible cAMP early repressor) is correlated with the inhibition and delay of CREB gene expression in the seminiferous tubules [7].

Anatomical context of Crem

• Preservation of spermatogenesis in spinal cord injured rats with exogenous testosterone. Relationship with serum testosterone levels and cellular localization of cAMP responsive element modulator [8].
• In granulosa cells, LH increases the expression of the inducible cAMP early repressor (ICER), an isoform of CREM (cAMP-responsive element modulator) that represses cAMP-induced transcription [9].

Associations of Crem with chemical compounds

• The administration of retinoic acid down-regulates cAMP-responsive element modulator (CREM) mRNA in vitamin A-deficient testes [6].
• As a further step toward understanding this process, we have studied the role of CREM in cocaine-induced testicular damage [10].

Other interactions of Crem

• These results suggest that retinoids function as a negative regulator of CREM expression in testes [6].

Analytical, diagnostic and therapeutic context of Crem

• Northern blot analysis revealed a 5-fold increase in the abundance of CREM-17X mRNA and a concomitant 50% reduction in the insulin mRNA in FFA-treated islets [1].
• In addition, RT-PCR analysis indicated that ATRA specifically represses the expression of the activator spliced variant of CREM (CREMtau) [6].
• Consistent with an inhibitory effect of CREM on CRH transcription, chromatin immunoprecipitation assays in cells transfected with ICER I revealed recruitment of CREM by the CRH promoter in conjunction with decreases in Pol II association [5].
• Using in situ hybridization with a cDNA fragment of the cAMP responsive element modulator (CREM) isoform inducible cAMP early repressor (ICER) we demonstrate a light-induced upregulation of CREM mRNA in rat SCN during the second half of the night [11].
• Western blot analysis using CREM antibodies confirmed the RNA data [10].

References