Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P56851 (epididymal)
 11,273 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This report presents data that suggest that the tissue-restricted polyoma enhancer activator protein (PEA3) of the Ets oncogene family of DNA-binding proteins is a putative modulator of the epididymis-specific glutathione peroxidase 5 gene gpx5. Northern and polymerase chain reactions on reverse-transcribed epididymal RNAs were used to show that the PEA3 factor is spatially and temporally expressed within the mouse epididymis in a manner consistent with gpx5 characteristics of expression. Then, using contransfection experiments carried out in heterologous tissue-culture cells with various deletions of the gpx5 promoter driving a CAT reporter gene, we have shown that the transcriptional activity of the gpx5 promoter is modulated by the presence of the PEA3 protein. Subsequently, we have shown using gel-shift assays that DNA sequences located within the 5' flanking region of the gpx5 gene have the ability to bind specifically to the PEA3 protein. Finally, using Northern assays we present data that suggest that PEA3 mRNA accumulation in the mouse caput epididymidis is controlled by androgens and testicular factors. Altogether, these results strongly suggest that the PEA3 factor might participate in the transcriptional control of the murine epididymis caput-specific gpx5 gene.
 ...
PMID:The PEA3 protein of the Ets oncogene family is a putative transcriptional modulator of the mouse epididymis-specific glutathione peroxidase gene gpx5. 944 56

Primary cultures of the differentiated, adult epididymal duct epithelium were immortalized by retroviral transduction with the simian virus (SV)40 large T antigen. The canine epididymis was chosen here as a model with high human relevance, representing a convenient and acceptable source of differentiated epididymal tissue and, compared to other animal models, expressing a relatively large number of gene products which are also expressed by the human epididymis. To determine whether the immortalized canine epididymal (IMCE) cells retained a phenotype comparable to the original tissue, epithelial cytokeratins, various epididymal transcription factors as well as mRNAs encoding abundant epididymal secretory proteins, were studied as molecular markers. All IMCE populations obtained after transduction were of epithelial origin. The nuclear androgen receptor (AR) and the polyoma enhancer activator (PEA3), as well as the epididymal mRNA encoding the canine counterparts of human HE1, HE4 and HE5/CD52 epididymal mRNA, were retained in all populations tested. The majority of tested clones were oestrogen receptor ERalpha-positive, but ERbeta-negative, while one ERalpha-negative cell population was positive for ERbeta. The IMCE populations described thus represent useful permanent tools for studying gene expression of the epididymal duct epithelium, and for other types of experiments, examples including drug effects and toxicity on the epididymis.
 ...
PMID:Epididymal epithelium immortalized by simian virus 40 large T antigen: a model to study epididymal gene expression. 1157 62

Transgenic male mice bearing inactive mutations of the receptor tyrosine kinase c-ros lack the initial segment of the epididymis and are infertile. Several techniques were applied to determine differences in gene expression in the epididymal caput of heterozygous fertile (HET) and infertile homozygous knockout (KO) males that may explain the infertility. Complementary DNA arrays, gene chips, Northern and Western blots, and immunohistochemistry indicated that some proteins were downregulated, including the initial segment/proximal caput-specific genes c-ros, cystatin-related epididymal-spermatogenic (CRES), and lipocalin mouse epididymal protein 17 (MEP17), whereas other caput-enriched genes (glutathione peroxidase 5, a disintegrin and metalloproteinase [ADAM7], bone morphogenetic proteins 7 and 8a, A-raf, CCAAT/enhancer binding protein beta, PEA3) were unchanged. Genes normally absent from the initial segment (gamma-glutamyltranspeptidase, prostaglandin D2 synthetase, alkaline phosphatase) were expressed in the undifferentiated proximal caput of the KO. More distally, lipocalin 2 (24p3), CRISP1 (formerly MEP7), PEBP (MEP9), and mE-RABP (MEP10) were unchanged in expression. Immunohistochemistry and Western blots confirmed the absence of CRES in epididymal tissue and fluid and the continued presence of CRES in spermatozoa of the KO mouse. The glutamate transporters EAAC1 (EAAT3) and EAAT5 were downregulated and upregulated, respectively. The genes of over 70 transporters, channels, and pores were detected in the caput epididymidis, but in the KO, only three were downregulated and six upregulated. The changes in these genes could affect sperm function by modifying the composition of epididymal fluid and explain the infertility of the KO males. These genes may be targets for a posttesticular contraceptive.
 ...
PMID:Gene and protein expression in the epididymis of infertile c-ros receptor tyrosine kinase-deficient mice. 1289 Jul 34

Several genes expressed in the initial segment of the epididymis depend on factors from the testis that reach the epididymis via the luminal system. These include gamma-glutamyl transpeptidase mRNA IV (Ggt_pr4), steroid 5 alpha reductase (Srd5a1), glutathione peroxidase 5 (Gpx5), and cystatin-related epididymal spermatogenic (Cst8) genes. Promoter analyses indicated that these genes contain several ETS DNA-binding sites. Members of the polyomavirus enhancer activator 3 (ETV4) family bind to ETS sites on the promoter of target genes to regulate transcription. In this study, the role of ETV4 family members (ETV4, ETV5, ETV1) in the transcription of initial segment specific genes was evaluated. All three ETV4 family mRNAs are expressed in the principal cells of the initial segment and depend upon the presence of testicular luminal fluid factors. ETV4 protein was localized to principal cell nuclei and displayed the highest expression in the most proximal region of the initial segment. In addition, ETV4 protein levels were diminished after loss of testicular luminal fluid factors. A dominant-negative construct of ETV5 was in vivo electroporated into the initial segment to determine if ETV4 family members can regulate the transcription of testicular luminal fluid factor-regulated genes. Quantitative PCR indicated that 1 day postelectroporation, all three ETV4 family member mRNAs were significantly decreased. In addition, Ggt_pr4, Srd5a1, and Gpx5 mRNA levels were also significantly decreased. The data suggest that ETV4 family members regulate their own expression, and that they regulate transcription of a subset of genes that are dependent upon testicular luminal fluid factors.
 ...
PMID:Putative regulation of expression of members of the Ets variant 4 transcription factor family and their downstream targets in the rat epididymis. 1639 17

Pannexins (PANXs) are channel-forming proteins implicated in cellular communication through the secretion of biomolecules, such as ATP and glutamate. PANX1 and PANX3 are expressed in the male rat reproductive tract and their levels are regulated by androgens in the epididymis. There is currently no information on the regulation of the Panx1 promoter. The objective of the present study was to characterize the Panx1 promoter in order to understand its regulation in the epididymis. RNA ligase-mediated rapid amplification of cDNA ends identified three transcriptional start sites, at positions -443, -429, and -393. In silico analysis revealed that transcription was initiated downstream of binding sites for CREB and ETV4 transcription factors, in a CpG island context. To determine the importance of this region in gene transactivation, a 2-kb fragment of the promoter was cloned into a vector containing a luciferase reporter gene. Deletion constructs indicated that the highest transactivation levels were achieved with shorter constructs (-973 to -346 and -550 to -346). Electrophoretic mobility shift assay and supershifts indicated that both transcription factors were able to bind to the promoter region. Chromatin immunoprecipitation using rat caput epididymis cells confirmed the binding of ETV4 and CREB on the Panx1 promoter. Site mutation of either the ETV4 or CREB binding site decreased the transactivation of the reporter gene. Previous studies indicated that orchidectomy increased epididymal PANX1 levels. Likewise, we observed an increase in both ETV4 and CREB in orchidectomized rats. These results indicate that ETV4 and cAMP response elements play a role in the transcriptional regulation of Panx1 in the epididymis.
...
PMID:Regulation of the pannexin-1 promoter in the rat epididymis. 2537 29