title: Alternative translation of osteopontin generates intracellular and secreted isoforms that mediate distinct biological activities in dendritic cells.
abstract: Osteopontin (Opn) contributes to diverse biological processes that include immune responses, vascularization, and bone formation. Until recently, studies describing the activities of Opn have focused on the cytokine-like properties of the secreted protein. Here, we show that alternative translation of a single Opn mRNA species generates a secreted and intracellular isoform. Utilization of a 5' canonical translation start site generates a protein that includes an N-terminal signal sequence allowing targeting to secretory vesicles and cytokine secretion, whereas usage of a downstream start site generates a shortened protein that lacks the N-terminal signal sequence and localizes mainly to cytoplasm. The coordinated action of these Opn gene products regulates the functional phenotype of subsets of dendritic cells.
authors.affiliation: Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston MA 02115, USA.
authors.forename: Mari L
authors.initials: ML
authors.lastname: Shinohara
authors.forename: Hye-Jung
authors.initials: HJ
authors.lastname: Kim
authors.forename: June-Ho
authors.initials: JH
authors.lastname: Kim
authors.forename: Virgilio A
authors.initials: VA
authors.lastname: Garcia
authors.forename: Harvey
authors.initials: H
authors.lastname: Cantor
mesh_terms: D017398:Alternative Splicing; D018899:CpG Islands; D003593:Cytoplasm / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology*; D017353:Gene Deletion; D005786:Gene Expression Regulation; D006801:Humans; D008954:Models, Biological; D008957:Models, Genetic; D053495:Osteopontin / Q000096:biosynthesis* / Q000235:genetics*; D010641:Phenotype; D020033:Protein Isoforms; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D020033:Protein Isoforms; D012333:RNA, Messenger; D053495:Osteopontin