Alternative translation of osteopontin generates intracellular and secreted isoforms that mediate distinct biological activities in dendritic cells.
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.
Shinohara
Mari L
ML
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston MA 02115, USA.
Kim
Hye-Jung
HJ
Kim
June-Ho
JH
Garcia
Virgilio A
VA
Cantor
Harvey
H
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
D020033:Protein Isoforms; D012333:RNA, Messenger; D053495:Osteopontin