dc.creator | Lian, Na | |
dc.date.accessioned | 2020-08-21T21:38:46Z | |
dc.date.available | 2012-04-14 | |
dc.date.issued | 2011-04-14 | |
dc.identifier.uri | https://etd.library.vanderbilt.edu/etd-03262011-122546 | |
dc.identifier.uri | http://hdl.handle.net/1803/11392 | |
dc.description.abstract | This project is concerned with mechanisms underlying osteoblast differentiation, a critical process during bone remodeling and repair. In this dissertation I explored novel regulators for osteoblast differentiation by identifying functional partners of ATF4, an osteoblast-enriched transcription factor important for osteoblast differentiation and bone formation. Through a combination of biochemical, molecular and cellular experiments, I identified and confirmed vimentin, an intermediate filament protein, as a novel inhibitor for ATF4's transcriptional activity and osteoblast differentiation. Furthermore, through series of genetic and pharmacological interventions in vitro and in vivo, I revealed that the vimentin serves as a downstream mediator that responds TGF beta signaling by binding and inhibiting ATF4 in immure osteoblasts via a non-canonical pathway. Therefore, this research uncovers a novel mechanism by which a cytoskeletal protein, vimentin, acts as a brake on differentiation in immature osteoblasts by its interaction with ATF4. | |
dc.format.mimetype | application/pdf | |
dc.subject | TGF beta | |
dc.subject | ATF4 | |
dc.subject | Vimentin | |
dc.subject | Bone. Osteoblast | |
dc.title | Vimentin, a novel regulator of the transcription factor ATF4 and osteoblast differentiation | |
dc.type | dissertation | |
dc.contributor.committeeMember | Xiangli Yang | |
dc.contributor.committeeMember | Florent Elefteriou | |
dc.contributor.committeeMember | Douglas Mortlock | |
dc.contributor.committeeMember | Eugenia Gurevich | |
dc.contributor.committeeMember | Linda Sealy | |
dc.type.material | text | |
thesis.degree.name | PHD | |
thesis.degree.level | dissertation | |
thesis.degree.discipline | Pharmacology | |
thesis.degree.grantor | Vanderbilt University | |
local.embargo.terms | 2012-04-14 | |
local.embargo.lift | 2012-04-14 | |
dc.contributor.committeeChair | Vsevolod Gurevich | |