http://purl.uniprot.org/citations/12552083 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
http://purl.uniprot.org/citations/12552083 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
http://purl.uniprot.org/citations/12552083 | http://www.w3.org/2000/01/rdf-schema#comment | "Phosphorylation-dependent ubiquitination combined with proteasomal degradation of transcriptional regulators is a recently appreciated mechanism for control of a number of inflammatory genes. Far less is known about the counterregulatory mechanisms that repress transcriptional activity in these pathways during resolution. Here, we investigated the transient nature of hypoxia-induced tumor necrosis factor (TNF)alpha in T84 cells, a process we have previously shown to involve phosphorylation-dependent degradation of the cAMP-response element-binding protein (CREB). Initial studies indicate hypoxia-induced TNFalpha to be a transient event, the resolution of which is associated with the appearance of a higher molecular weight modified form of CREB. Gene array analysis of mRNA derived from hypoxic cells identified a time-dependent induction of small ubiquitin-related modifier (SUMO)-1 mRNA. In prolonged hypoxia, CREB is posttranslationally modified by SUMO-1. Furthermore, SUMO-1 overexpression stabilizes CREB in hypoxia and enhances CREB-dependent reporter gene activity. Site-directed mutagenesis of lysine residues K285 and K304 identifies them as SUMO acceptors in vivo and in vitro. Mutation of K304 also results in loss of CREB nuclear localization, implying a role for SUMO-1 modification at this site in the subcellular localization of CREB. Thus, in prolonged hypoxia, CREB is modified by association with SUMO-1. Furthermore, we hypothesize that such an event stabilizes and promotes nuclear localization of CREB and thus complements an endogenous resolution phase for hypoxia-induced inflammatory processes."xsd:string |
http://purl.uniprot.org/citations/12552083 | http://purl.org/dc/terms/identifier | "doi:10.1073/pnas.0337412100"xsd:string |
http://purl.uniprot.org/citations/12552083 | http://purl.org/dc/terms/identifier | "doi:10.1073/pnas.0337412100"xsd:string |
http://purl.uniprot.org/citations/12552083 | http://purl.uniprot.org/core/author | "Colgan S.P."xsd:string |
http://purl.uniprot.org/citations/12552083 | http://purl.uniprot.org/core/author | "Colgan S.P."xsd:string |
http://purl.uniprot.org/citations/12552083 | http://purl.uniprot.org/core/author | "Karhausen J."xsd:string |
http://purl.uniprot.org/citations/12552083 | http://purl.uniprot.org/core/author | "Karhausen J."xsd:string |
http://purl.uniprot.org/citations/12552083 | http://purl.uniprot.org/core/author | "Carey R."xsd:string |
http://purl.uniprot.org/citations/12552083 | http://purl.uniprot.org/core/author | "Carey R."xsd:string |
http://purl.uniprot.org/citations/12552083 | http://purl.uniprot.org/core/author | "Comerford K.M."xsd:string |
http://purl.uniprot.org/citations/12552083 | http://purl.uniprot.org/core/author | "Comerford K.M."xsd:string |
http://purl.uniprot.org/citations/12552083 | http://purl.uniprot.org/core/author | "Leonard M.O."xsd:string |
http://purl.uniprot.org/citations/12552083 | http://purl.uniprot.org/core/author | "Leonard M.O."xsd:string |
http://purl.uniprot.org/citations/12552083 | http://purl.uniprot.org/core/author | "Taylor C.T."xsd:string |
http://purl.uniprot.org/citations/12552083 | http://purl.uniprot.org/core/author | "Taylor C.T."xsd:string |
http://purl.uniprot.org/citations/12552083 | http://purl.uniprot.org/core/date | "2003"xsd:gYear |
http://purl.uniprot.org/citations/12552083 | http://purl.uniprot.org/core/date | "2003"xsd:gYear |
http://purl.uniprot.org/citations/12552083 | http://purl.uniprot.org/core/name | "Proc. Natl. Acad. Sci. U.S.A."xsd:string |
http://purl.uniprot.org/citations/12552083 | http://purl.uniprot.org/core/name | "Proc. Natl. Acad. Sci. U.S.A."xsd:string |
http://purl.uniprot.org/citations/12552083 | http://purl.uniprot.org/core/pages | "986-991"xsd:string |
http://purl.uniprot.org/citations/12552083 | http://purl.uniprot.org/core/pages | "986-991"xsd:string |
http://purl.uniprot.org/citations/12552083 | http://purl.uniprot.org/core/title | "Small ubiquitin-related modifier-1 modification mediates resolution of CREB-dependent responses to hypoxia."xsd:string |
http://purl.uniprot.org/citations/12552083 | http://purl.uniprot.org/core/title | "Small ubiquitin-related modifier-1 modification mediates resolution of CREB-dependent responses to hypoxia."xsd:string |