title: DSPP contains an IRES element responsible for the translation of dentin phosphophoryn.
abstract: The major phosphoprotein in dentin is the aspartic acid and serine-rich protein called dentin phosphophoryn (DPP). DPP appears to be synthesized as a part of a larger compound protein, dentin sialophosphoprotein (DSPP). DSPP has never been isolated or detected in dentin extracts. It is now evident that DSPP is a chimeric protein composed of 3 parts: dentin sialoprotein (DSP), DPP, and dentin glycoprotein (DGP). Previous reports have suggested that the BMP1 protease is responsible for processing DSPP. However, unequal amounts of these products are present in the dentin matrix. Here, we provide evidence for an internal ribosome entry site in the DSPP gene that directs the synthesis of DPP. This mechanism would account for unequal amounts of intracellular DSP and DPP. The internal ribosomal entry site (IRES) activity varied in different cell types, suggesting the presence of additional regulatory elements during the translational regulation of DPP. Further, we provide evidence that DPP is transported to the extracellular matrix (ECM) through exosomes. Using tissue recombination and lentivirus-mediated gain-of-function approaches, we also demonstrate that DPP is essential for the formation of well-defined tooth structures with mineralized dentin matrix.
authors.affiliation: Brodie Tooth Development Genetics & Regenerative Medicine Research Laboratory, Department of Oral Biology, University of Illinois at Chicago, Chicago, IL 60612, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.forename: Y
authors.initials: Y
authors.lastname: Song
authors.forename: S
authors.initials: S
authors.lastname: Ravindran
authors.forename: Q
authors.initials: Q
authors.lastname: Gao
authors.forename: C C
authors.initials: CC
authors.lastname: Huang
authors.forename: A
authors.initials: A
authors.lastname: Ramachandran
authors.forename: A
authors.initials: A
authors.lastname: Kulkarni
authors.forename: A
authors.initials: A
authors.lastname: George
mesh_terms: D016475:3T3 Cells; D000818:Animals; D002460:Cell Line; D003782:Dental Pulp / Q000166:cytology; D003804:Dentin / Q000648:ultrastructure; D003810:Dentinogenesis / Q000235:genetics; D055354:Exosomes / Q000378:metabolism; D005109:Extracellular Matrix / Q000648:ultrastructure; D016326:Extracellular Matrix Proteins / Q000235:genetics* / Q000378:metabolism; D005822:Genetic Vectors / Q000235:genetics; D057809:HEK293 Cells; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism; D010957:Plasmids / Q000235:genetics; D014176:Protein Biosynthesis / Q000235:genetics*; D046188:Protein Modification, Translational / Q000235:genetics; D050436:Regulatory Elements, Transcriptional / Q000235:genetics; D012270:Ribosomes / Q000235:genetics*; D012795:Sialoglycoproteins / Q000235:genetics* / Q000378:metabolism; D013539:Simian virus 40 / Q000235:genetics; D013234:Stem Cells / Q000166:cytology; D000099311:Dentin Sialophosphoprotein
chemical_list: D016326:Extracellular Matrix Proteins; D010750:Phosphoproteins; D012795:Sialoglycoproteins; D000099311:Dentin Sialophosphoprotein
keywords: cell biology; cell differentiation; dentin; extracellular matrix (ECM); matrix biology; odontoblast(s)