| http://purl.uniprot.org/citations/16449647 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/16449647 | http://www.w3.org/2000/01/rdf-schema#comment | "Gamma-secretase, which is responsible for the intramembranous cleavage of Alzheimer's beta-amyloid precursor protein (APP), the signaling receptor Notch, and many other substrates, is a multiprotein complex consisting of at least four components: presenilin (PS), nicastrin, APH-1, and PEN-2. Despite the fact that PEN-2 is known to mediate endoproteolytic cleavage of full-length PS and APH-1 and nicastrin are required for maintaining the stability of the complex, the detailed physiological function of each component remain elusive. Unlike that of PS, the transcriptional regulation of PEN-2, APH-1, and nicastrin has not been investigated. Here, we characterized the upstream regions of the human PEN-2 gene and identified a 238-bp fragment located 353 bp upstream of the translational start codon as the key region necessary for the promoter activity. Further analysis revealed a CREB binding site located in the 238-bp region that is essential for the transcriptional activity of the PEN-2 promoter. Mutation of the CREB site abolished the transcriptional activity of the PEN-2 promoter. Electrophoretic mobility shift assays and chromatin immunoprecipitation analysis showed the binding of CREB to the PEN-2 promoter region both in vitro and in vivo. Activation of the CREB transcriptional factor by forskolin dramatically promoted the expression of PEN-2 mRNA and protein, whereas the other components of the gamma-secretase complex remained unaffected. Forskolin treatment slightly increases the secretion of soluble APPalpha and Abeta without affecting Notch cleavage. These results demonstrate that expression of PEN-2 is regulated by CREB and suggest that the specific control of PEN-2 expression may imply additional physiological functions uniquely assigned to PEN-2."xsd:string |
| http://purl.uniprot.org/citations/16449647 | http://purl.org/dc/terms/identifier | "doi:10.1128/mcb.26.4.1347-1354.2006"xsd:string |
| http://purl.uniprot.org/citations/16449647 | http://purl.uniprot.org/core/author | "Liu R."xsd:string |
| http://purl.uniprot.org/citations/16449647 | http://purl.uniprot.org/core/author | "Zhang X."xsd:string |
| http://purl.uniprot.org/citations/16449647 | http://purl.uniprot.org/core/author | "Xu H."xsd:string |
| http://purl.uniprot.org/citations/16449647 | http://purl.uniprot.org/core/author | "Zhang Z."xsd:string |
| http://purl.uniprot.org/citations/16449647 | http://purl.uniprot.org/core/author | "Wang R."xsd:string |
| http://purl.uniprot.org/citations/16449647 | http://purl.uniprot.org/core/author | "Xia J."xsd:string |
| http://purl.uniprot.org/citations/16449647 | http://purl.uniprot.org/core/author | "Sun P."xsd:string |
| http://purl.uniprot.org/citations/16449647 | http://purl.uniprot.org/core/author | "Zhang X.'"xsd:string |
| http://purl.uniprot.org/citations/16449647 | http://purl.uniprot.org/core/author | "Xia K."xsd:string |
| http://purl.uniprot.org/citations/16449647 | http://purl.uniprot.org/core/author | "Zhang Y.W."xsd:string |
| http://purl.uniprot.org/citations/16449647 | http://purl.uniprot.org/core/date | "2006"xsd:gYear |
| http://purl.uniprot.org/citations/16449647 | http://purl.uniprot.org/core/name | "Mol Cell Biol"xsd:string |
| http://purl.uniprot.org/citations/16449647 | http://purl.uniprot.org/core/pages | "1347-1354"xsd:string |
| http://purl.uniprot.org/citations/16449647 | http://purl.uniprot.org/core/title | "Transcriptional regulation of PEN-2, a key component of the gamma-secretase complex, by CREB."xsd:string |
| http://purl.uniprot.org/citations/16449647 | http://purl.uniprot.org/core/volume | "26"xsd:string |
| http://purl.uniprot.org/citations/16449647 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/16449647 |
| http://purl.uniprot.org/citations/16449647 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/16449647 |
| http://purl.uniprot.org/uniprot/#_B7Z7P1-mappedCitation-16449647 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/16449647 |
| http://purl.uniprot.org/uniprot/#_B7Z5C6-mappedCitation-16449647 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/16449647 |
| http://purl.uniprot.org/uniprot/#_Q16118-mappedCitation-16449647 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/16449647 |
| http://purl.uniprot.org/uniprot/#_Q53X93-mappedCitation-16449647 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/16449647 |
| http://purl.uniprot.org/uniprot/#_P16220-mappedCitation-16449647 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/16449647 |