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Title page for ETD etd-03262011-122546


Type of Document Dissertation
Author Lian, Na
URN etd-03262011-122546
Title Vimentin, a novel regulator of the transcription factor ATF4 and osteoblast differentiation
Degree PhD
Department Pharmacology
Advisory Committee
Advisor Name Title
Vsevolod Gurevich Committee Chair
Douglas Mortlock Committee Member
Eugenia Gurevich Committee Member
Florent Elefteriou Committee Member
Linda Sealy Committee Member
Xiangli Yang Committee Member
Keywords
  • TGF beta
  • ATF4
  • Vimentin
  • Bone. Osteoblast
Date of Defense 2010-12-09
Availability unrestricted
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.
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