| http://purl.uniprot.org/citations/15122901 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/15122901 | http://www.w3.org/2000/01/rdf-schema#comment | "Mammalian presenilins (PS) consist of two highly homologous proteins, PS1 and PS2. Because of their indispensable activity in the gamma-secretase cleavage of amyloid precursor protein to generate Abeta peptides, inhibition of PS gamma-secretase activity is considered a potential therapy for Abeta blockage and Alzheimer's disease intervention. However, a variety of other substrates are also subject to PS-dependent processing, and it is thus imperative to understand the consequences of PS inactivation in vivo. Here we report a pivotal role of PS in hematopoiesis. Mice heterozygous for PS1 and homozygous for PS2 (PS1(+/)(-)PS2(-)(/)(-)) developed splenomegaly with severe granulocyte infiltration. This was preceded by an overrepresentation of granulocytic cells in the bone marrow and a greatly increased multipotent granulocyte-monocyte progenitor in the spleen. In contrast, hematopoietic stem cells and T- and B-lymphocytes were not affected. Importantly, treatment of wild-type splenocytes with a gamma-secretase inhibitor directly promoted the granulocyte-macrophage colony-forming unit (GM-CFU). These results establish a critical role of PS in myelopoiesis. Our finding that this activity can be directly modulated by its gamma-secretase activity has important safety implications concerning these inhibitors."xsd:string |
| http://purl.uniprot.org/citations/15122901 | http://purl.org/dc/terms/identifier | "doi:10.1021/bi049826u"xsd:string |
| http://purl.uniprot.org/citations/15122901 | http://purl.uniprot.org/core/author | "Chen X."xsd:string |
| http://purl.uniprot.org/citations/15122901 | http://purl.uniprot.org/core/author | "Wang P."xsd:string |
| http://purl.uniprot.org/citations/15122901 | http://purl.uniprot.org/core/author | "Zheng H."xsd:string |
| http://purl.uniprot.org/citations/15122901 | http://purl.uniprot.org/core/author | "Xia X."xsd:string |
| http://purl.uniprot.org/citations/15122901 | http://purl.uniprot.org/core/author | "Qyang Y."xsd:string |
| http://purl.uniprot.org/citations/15122901 | http://purl.uniprot.org/core/author | "Goodell M.A."xsd:string |
| http://purl.uniprot.org/citations/15122901 | http://purl.uniprot.org/core/author | "Chambers S.M."xsd:string |
| http://purl.uniprot.org/citations/15122901 | http://purl.uniprot.org/core/date | "2004"xsd:gYear |
| http://purl.uniprot.org/citations/15122901 | http://purl.uniprot.org/core/name | "Biochemistry"xsd:string |
| http://purl.uniprot.org/citations/15122901 | http://purl.uniprot.org/core/pages | "5352-5359"xsd:string |
| http://purl.uniprot.org/citations/15122901 | http://purl.uniprot.org/core/title | "Myeloproliferative disease in mice with reduced presenilin gene dosage: effect of gamma-secretase blockage."xsd:string |
| http://purl.uniprot.org/citations/15122901 | http://purl.uniprot.org/core/volume | "43"xsd:string |
| http://purl.uniprot.org/citations/15122901 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/15122901 |
| http://purl.uniprot.org/citations/15122901 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/15122901 |
| http://purl.uniprot.org/uniprot/Q61144#attribution-E0913A9BEA6744521EDE6A676C728305 | http://purl.uniprot.org/core/source | http://purl.uniprot.org/citations/15122901 |
| http://purl.uniprot.org/uniprot/P49769#attribution-E0913A9BEA6744521EDE6A676C728305 | http://purl.uniprot.org/core/source | http://purl.uniprot.org/citations/15122901 |
| http://purl.uniprot.org/uniprot/#_A0A087WRQ4-mappedCitation-15122901 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/15122901 |
| http://purl.uniprot.org/uniprot/#_A0A0R4J1F2-mappedCitation-15122901 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/15122901 |
| http://purl.uniprot.org/uniprot/#_D3Z0X1-mappedCitation-15122901 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/15122901 |
| http://purl.uniprot.org/uniprot/#_Q3U4P5-mappedCitation-15122901 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/15122901 |
| http://purl.uniprot.org/uniprot/#_P49769-mappedCitation-15122901 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/15122901 |
| http://purl.uniprot.org/uniprot/#_P63166-mappedCitation-15122901 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/15122901 |