Disease relevance of Crem

• The disruption of CREM gene expression in crem null mice results in arrest of spermatogenesis and infertility [1].

Psychiatry related information on Crem

• No maternal behavior phenotype was present in mice with a null mutation of the cyclic AMP response element modulator (Crem) gene [2].

High impact information on Crem

• CREM regulates many crucial genes required for spermatid maturation, and targeted mutation of the Crem gene in the mouse germ-line blocks spermatogenesis [3].
• Abnormal sperm in mice with targeted deletion of the act (activator of cAMP-responsive element modulator in testis) gene [3].
• Protein expression of transition proteins 1 and 2 and angiotensin-converting enzyme was completely absent, whereas that of the transcriptional activator cAMP responsive element modulator was intact [4].
• The kinesin KIF17b and RNA-binding protein TB-RBP transport specific cAMP-responsive element modulator-regulated mRNAs in male germ cells [5].
• We have previously documented a striking, clock-driven circadian fluctuation of CREM expression in the pineal gland [6].

Biological context of Crem

• Tax binds to enhancer-binding proteins including cAMP-responsive element-binding protein, cAMP-responsive element modulator, transcription factor NF-kappa B p50 and p67SRF, and associates with each enhancer DNA indirectly [7].
• S-CREM shares with the other CREM proteins the basic DNA-binding and leucine-zipper dimerization domain [8].
• Induction of CREM activator proteins in spermatids: down-stream targets and implications for haploid germ cell differentiation [9].
• Phosphorylation of serine-117 turns CREM tau into a powerful activator [9].
• The rise in CREM tau protein coincides with the transcriptional activation of several genes [9].

Anatomical context of Crem

• Differential activation of viral and cellular promoters by human T-cell lymphotropic virus-1 tax and cAMP-responsive element modulator isoforms [10].
• Analysis ex vivo of CREM gene expression in temporally staged segments of the seminiferous tubule during the spermatogenic cycle shows that the activities of the P1, P3, and P4 promoters are independently regulated [1].
• In mouse testis, several CREM repressors and activators have been identified [11].
• CREM activator expression was confined to the testis, where it was seen in late pachytene spermatocytes and round spermatids in specific spermatogenic stages, as revealed by in situ hybridization [11].
• Identification of novel cAMP responsive element modulator (CREM) isoforms expressed by osteoblasts [12].

Chemical compound and disease context of Crem

• In a murine model of endotoxemia, CGRP markedly attenuated serum TNF-alpha levels, and this effect was associated with the up-regulation of ICER [13].

Associations of Crem with chemical compounds

• We show that CREM tau is efficiently phosphorylated at a serine residue at position 117 by the protein kinase-A endogenous to germ cells, indicating that it constitutes a natural target of the adenylyl cyclase pathway during spermatogenesis [9].
• Mice lacking the functional cAMP responsive element modulator (CREM) gene, a component of cAMP-mediated signal transduction, exhibit a specific arrest of round spermatid development although follicle stimulating hormone (FSH) and androgen secretion are not impaired [14].

Analytical, diagnostic and therapeutic context of Crem

• In particular, we determined by RT-PCR that a switch from the expression of CREM repressors to CREM activators is present in postmeiotic germ cells in normospermic men [15].

References