Functional characterization of male germ cell-specific CREM isoforms.

Due to alternative promoter usage, splicing, and translational initiation, expression of the cAMP-responsive element modulator (CREM) gene results in the production of functionally different CREM proteins with either activating or repressing potential on target gene expression. Recently, we demonstrated 2 novel isoforms (CREM-2-F-G-H-Ib and CREM-2-G-H-Ib) in various germ cell types during normal and impaired human spermatogenesis. In contrast to known isoforms, these exhibit a transactivation domain but lack a kinase-inducible domain (KID) domain resulting in a disruption of the open reading frame.

Physical interaction and mutual transrepression between CCAAT/enhancer-binding protein beta and the p53 tumor suppressor.

The tumor suppressor protein p53 is not only involved in defending cells against genotoxic insults but is also implicated in differentiation processes, a function that it shares with the CCAAT/enhancer-binding protein beta (C/EBPbeta). We previously reported an up-regulation of both factors in the cycle-dependent differentiation process of human endometrial stromal cells, termed decidualization. C/EBPbeta-mediated activation of a decidualization marker, the decidual prolactin promoter, was antagonized by p53.

Wild-type p53 protein is up-regulated upon cyclic adenosine monophosphate-induced differentiation of human endometrial stromal cells.

Decidualization of the endometrial stromal compartment is critical for embryo implantation. Initiation of this differentiation process requires elevated intracellular cAMP levels. We now report a massive and sustained up-regulation of p53 tumor suppressor protein during cAMP-induced decidualization of cultured endometrial stromal cells.

Novel leader exons of the cyclic adenosine 3',5'-monophosphate response element modulator (CREM) gene, transcribed from promoters P3 and P4, are highly testis-specific in primates.

Testicular expression of CREM is essential for spermatogenesis in the mouse. From a monkey testis cDNA library we isolated a CREM transcript isoform with a novel 5' exon theta2 which provides at its 3'-end an in-frame ATG to the downstream reading frame. 5'-RACE on human testis cDNA indicated that exon theta2 is > or = 113 bp in size.

Functional association of PR and CCAAT/enhancer-binding protein beta isoforms: promoter-dependent cooperation between PR-B and liver-enriched inhibitory protein, or liver-enriched activatory protein and PR-A in human endometrial stromal cells.

Activation of the decidual PRL (dPRL) promoter, a major differentiation marker in human endometrial stromal (ES) cells, by cAMP is effected through the induction and binding of CCAAT/enhancer-binding protein-beta (C/EBPbeta) to two overlapping cognate response elements in the promoter region dPRL-332/-270. Progesterone is essential for decidualization and potently enhances cAMP-dependent dPRL promoter activity. We now demonstrate that both liganded PR isoforms, PR-A and PR-B, are capable of trans-activating the dPRL-332/-270 region.