FIAT control of osteoblast activity

St‐Arnaud, René; Mandic, Vice

doi:10.1002/jcb.22435

Cited by 5 publications

(3 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…ATF4 regulates OCN expression positively by binding to osteocalcin-specific element (OSE1), and it interacts cooperatively with Runx2 through SATB2. 92 , 94 , 95 Factors inhibiting ATF4-mediated transcription (Fiat) have been found to suppress ATF4 activity and, co-expressed in osteoblasts 96 , 97 and modulated by the Sp family, to exclude Osx. 98 In the matrix mineralization stage, ATF4 is positively regulated, to a large extent, by c-Jun N-terminal kinase (JNK), affecting the expression of OCN and BSP.…”

Section: Mirnas In Osteoblast Lineage and Bone Formationmentioning

confidence: 99%

The role of microRNAs in bone remodeling

et al. 2015

View full text Add to dashboard Cite

Bone remodeling is balanced by bone formation and bone resorption as well as by alterations in the quantities and functions of seed cells, leading to either the maintenance or deterioration of bone status. The existing evidence indicates that microRNAs (miRNAs), known as a family of short non-coding RNAs, are the key post-transcriptional repressors of gene expression, and growing numbers of novel miRNAs have been verified to play vital roles in the regulation of osteogenesis, osteoclastogenesis, and adipogenesis, revealing how they interact with signaling molecules to control these processes. This review summarizes the current knowledge of the roles of miRNAs in regulating bone remodeling as well as novel applications for miRNAs in biomaterials for therapeutic purposes.

show abstract

Section: Mirnas In Osteoblast Lineage and Bone Formationmentioning

confidence: 99%

The role of microRNAs in bone remodeling

et al. 2015

View full text Add to dashboard Cite

show abstract

“…FIAT (Factor Inhibiting ATF4‐mediated Transcription, also named γ‐taxilin) is a leucine‐zipper protein devoid of DNA‐binding activity but capable of heterodimerizing with ATF4 to form inactive dimers and inhibit ATF4 transcriptional activity [Yu et al, ; St‐Arnaud and Mandic, ]. The exhaustive phenotype analysis of FIAT transgenic mice [Yu et al, ] combined with a number of in vitro experiments [Yu et al, , , ] support the interpretation that FIAT interacts with ATF4 to repress its transcriptional activity, thus regulating bone mass.…”

mentioning

confidence: 99%

SUMOylated αNAC Potentiates Transcriptional Repression by FIAT

Hekmatnejad

Akhouayri

Jafarov

et al. 2014

J of Cellular Biochemistry

Self Cite

View full text Add to dashboard Cite

The transcriptional coregulator αNAC (Nascent polypeptide associated complex And Coregulator alpha) and the transcriptional repressor FIAT (Factor Inhibiting ATF4-mediated Transcription) interact but the biological relevance of this interaction remains unclear. The activity of αNAC is extensively modulated by post-translational modifications (PTMs). We identified a novel αNAC PTM through covalent attachment of the Small Ubiquitin-like MOdifier (SUMO1). Recombinant αNAC was a SUMO1 target in in vitro SUMOylation assays and we confirmed that αNAC is conjugated to SUMO1 in cultured osteoblasts and in calvarial tissue. The amino acid sequence of αNAC contains one copy of the composite "phospho-sumoyl switch" motif that couples sequential phosphorylation and SUMOylation. We found that αNAC is selectively SUMOylated at lysine residue 127 within the motif and that SUMOylation is enhanced when a phosphomimetic mutation is introduced at the nearby serine residue 132. SUMOylation did not alter the DNA-binding capacity of αNAC. The S132D, hyper-SUMOylated αNAC mutant specifically interacted with histone deacetylase-2 (HDAC2) and enhanced the inhibitory activity of FIAT on ATF4-mediated transcription from the Osteocalcin gene promoter. This effect required binding of SUMOylated αNAC to the target promoter. We propose that maximal transcriptional repression by FIAT requires its interaction with SUMOylated, HDAC2-interacting αNAC.

show abstract

“…During osteogenesis FIAT regulates osteoblast biology by interacting with ATF4 and inhibiting its function [Yu et al, 2005, 2009b]. ATF4 is a key transcription factor that controls the expression of critical effectors of osteoblast activity including Esp , Rankl , and Osteocalcin [Karsenty, 2008; St‐Arnaud and Mandic, 2010]. This regulatory role of FIAT makes it important to understand how Fiat transcription and expression is controlled.…”

Section: Discussionmentioning

confidence: 99%

Control of Fiat (factor inhibiting ATF4‐mediated transcription) expression by Sp family transcription factors in osteoblasts

Hekmatnejad

Gauthier

St‐Arnaud

2013

J of Cellular Biochemistry

View full text Add to dashboard Cite

FIAT (factor inhibiting ATF4-mediated transcription) represses Osteocalcin gene transcription and inhibits osteoblast activity by heterodimerizing with ATF4 to prevent it from binding DNA. It thus appears important to identify and characterize the molecular mechanisms that control Fiat gene expression in osteoblasts. In silico sequence analysis identified a canonical GC-box within a 1,400 bp region of the proximal Fiat gene promoter. Electrophoretic mobility shift assays (EMSA) with MC3T3-E1 osteoblastic cells nuclear extracts indicated that the transcription factors Sp1 and Sp3, but not Sp7/OSTERIX, bound this proximal GC-box. Chromatin immunoprecipitation confirmed interaction of the two transcription factors with the Fiat promoter GC-element in living osteoblasts. Transient transfection studies showed that Sp1 dose-dependently activated the expression of a Fiat-luciferase reporter construct while both the long or short isoforms of Sp3 dose-dependently inhibited transcription from the Fiat reporter construct. Transfection of an Sp7/OSTERIX expression vector did not affect expression of the Fiat-luciferase reporter. Co-transfection of increasing amounts of the Sp3 expression vector in the context of maximal Sp1-dependent Fiat-luciferase activation led to dose-dependent repression of the expression of the reporter. Using RNA knockdown, we measured a reduction in steady-state Fiat expression when Sp1 was inhibited, and a reciprocal increase upon Sp3 knockdown. In parallel, treatment of osteoblasts with WP631, which prevents Sp1/DNA interactions, strongly inhibited the expression of Fiat and reduced the occupancy of the Fiat promoter proximal GC-box by Sp1. Taken together, our results suggest an interplay between Sp1 and Sp3 as a mechanism involved in the control of Fiat gene expression in osteoblasts.

show abstract

FIAT control of osteoblast activity

Cited by 5 publications

References 49 publications

The role of microRNAs in bone remodeling

The role of microRNAs in bone remodeling

SUMOylated αNAC Potentiates Transcriptional Repression by FIAT

Control of Fiat (factor inhibiting ATF4‐mediated transcription) expression by Sp family transcription factors in osteoblasts

Contact Info

Product

Resources

About