αNAC Requires an Interaction With c-Jun to Exert its Transcriptional Coactivation

Quélo, Isabelle; Hurtubise, Mélanie; St‐Arnaud, René

doi:10.3727/000000002783992433

Cited by 22 publications

(22 citation statements)

References 27 publications

(11 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, the possibility cannot be excluded that this mechanism is involved in the cytosolic retention of other factors important for erythroid cell maturation. NACA is also known as a coactivator of c-JUN-mediated transcription in developing bone during embryogenesis Quelo et al, 2002). However, because c-JUN behaves as a negative regulator of erythropoiesis (Elagib et al, 2004), the positive effect of NACA on erythroid-cell maturation cannot be explained by its c-JUN-mediated positive contribution.…”

Section: Discussionmentioning

confidence: 99%

NACA is a positive regulator of human erythroid-cell differentiation

Lopez

Stuhl

Fichelson

et al. 2005

Journal of Cell Science

View full text Add to dashboard Cite

We have previously identified the transcript encoding NACA (the α chain of the nascent-polypeptide-associated complex) as a cytokine-modulated specific transcript in the human TF-1 erythroleukemic cell line. This protein was already known to be a transcriptional co-activator that acts by potentiating AP-1 activity in osteoblasts, and is known to be involved in the targeting of nascent polypeptides. In this study, we investigate the role of NACA in human hematopoiesis. Protein distribution analyses indicate that NACA is expressed in undifferentiated TF-1 cells and in human-cord-blood-derived CD34+ progenitor cells. Its expression is maintained during in vitro erythroid differentiation but, in marked contrast, its expression is suppressed during their megakaryocytic or granulocytic differentiation. Ectopic expression of NACA in CD34+ cells under culture conditions that induce erythroid-lineage differentiation leads to a marked acceleration of erythroid-cell differentiation. Moreover, ectopic expression of NACA induces erythropoietin-independent differentiation of TF-1 cells, whereas downregulation of NACA by RNA interference abolishes the induction of hemoglobin production in these cells and diminishes glycophorin-A (GPA) expression by CD34+ progenitors cultured under erythroid differentiation conditions. Altogether, these results characterize NACA as a new factor involved in the positive regulation of human erythroid-cell differentiation.

show abstract

Section: Discussionmentioning

confidence: 99%

NACA is a positive regulator of human erythroid-cell differentiation

Lopez

Stuhl

Fichelson

et al. 2005

Journal of Cell Science

View full text Add to dashboard Cite

show abstract

“…We have engineered a series of C-terminal and internal deletion mutants of the ␣NAC protein (37,38) and tested them for DNA-binding activity with EMSA (data not shown). …”

Section: Resultsmentioning

confidence: 99%

“…We have previously shown that ␣NAC functions as a c-Jun coactivator (30,(36)(37)(38). The cloning of ␣NAC as a differentially expressed gene product in terminally differentiated osteoblasts (47) and the expression of the ␣NAC protein in mineralizing osteoblasts at the ossification centers of developing embryos (30) suggested that ␣NAC should be involved in some aspects of the regulation of gene transcription in differentiated bone-forming cells.…”

Section: Discussionmentioning

confidence: 99%

“…One such coactivator has been characterized as ␣NAC (30,(36)(37)(38). The ␣NAC protein, first identified as a regulator of protein translation (45), was subsequently shown to also function as a transcriptional coactivator by potentiating the activities of the chimeric Gal4-VP16 activator (47) and of c-Jun homodimers (30,(36)(37)(38). ␣NAC provides a protein bridge between c-Jun and the basal transcriptional machinery by contacting the general transcription factor TBP (47).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Sequence-Specific DNA Binding by the αNAC Coactivator Is Required for Potentiation of c-Jun-Dependent Transcription of the Osteocalcin Gene

Akhouayri

Quélo

St‐Arnaud

2005

Molecular and Cellular Biology

View full text Add to dashboard Cite

Since the c-Jun coactivator ␣NAC was initially identified in a differential screen for genes expressed in differentiated osteoblasts, we examined whether the osteocalcin gene, a specific marker of terminal osteoblastic differentiation, could be a natural target for the coactivating function of ␣NAC. We had also previously shown that ␣NAC can specifically bind DNA in vitro, but it remained unclear whether the DNA-binding function of ␣NAC is expressed in vivo or if it is required for coactivation. We have identified an ␣NAC binding site within the murine osteocalcin gene proximal promoter region and demonstrated that recombinant ␣NAC or ␣NAC from ROS17/2.8 nuclear extracts can specifically bind this element. Using transient transfection assays, we have shown that ␣NAC specifically potentiated the c-Jun-dependent transcription of the osteocalcin promoter and that this activity specifically required the DNA-binding domain of ␣NAC. Chromatin immunoprecipitation confirmed that ␣NAC occupies its binding site on the osteocalcin promoter in living osteoblastic cells expressing osteocalcin. Inhibition of the expression of endogenous ␣NAC in osteoblastic cells by use of RNA interference provoked a decrease in osteocalcin gene transcription. Our results show that the osteocalcin gene is a target for the ␣NAC coactivating function, and we propose that ␣NAC is specifically targeted to the osteocalcin promoter through its DNA-binding activity as a means to achieve increased specificity in gene transcription.

show abstract

“…CREB then stimulates the transcription of members of genes coding for the AP-1 family of basic domain- leucine zipper transcription factors, c-Fos and c-Jun (38)(39)(40). While the importance of AP-1 proteins in mediating the anabolic PTH response remains to be determined, it is noteworthy that ␣NAC interacts with the N-terminal activation domain of c-JUN to regulate transcription (16,20,21,41). Interaction with c-JUN involves residues 89 to 129 within ␣NAC (41), a region containing 5 ␤-sheets (42).…”

Section: Discussionmentioning

confidence: 99%

The PTH-Gα_s-Protein Kinase A Cascade Controls αNAC Localization To Regulate Bone Mass

Pellicelli

Miller

Arabian

et al. 2014

Molecular and Cellular Biology

View full text Add to dashboard Cite

The binding of PTH to its receptor induces G␣ s -dependent cyclic AMP (cAMP) accumulation to turn on effector kinases, including protein kinase A (PKA). The phenotype of mice with osteoblasts specifically deficient for G␣ s is mimicked by a mutation leading to cytoplasmic retention of the transcriptional coregulator ␣NAC, suggesting that G␣ s and ␣NAC form part of a common genetic pathway. We show that treatment of osteoblasts with PTH(1-34) or the PKA-selective activator N 6 -benzoyladenosine cAMP (6Bnz-cAMP) leads to translocation of ␣NAC to the nucleus. ␣NAC was phosphorylated by PKA at serine 99 in vitro. Phospho-S99-␣NAC accumulated in osteoblasts exposed to PTH(1-34) or 6Bnz-cAMP but not in treated cells expressing dominant-negative PKA. Nuclear accumulation was abrogated by an S99A mutation but enhanced by a phosphomimetic residue (S99D). Chromatin immunoprecipitation (ChIP) analysis showed that PTH(1-34) or 6Bnz-cAMP treatment leads to accumulation of ␣NAC at the Osteocalcin (Ocn) promoter. Altered gene dosages for G␣ s and ␣NAC in compound heterozygous mice result in reduced bone mass, increased numbers of osteocytes, and enhanced expression of Sost. Our results show that ␣NAC is a substrate of PKA following PTH signaling. This enhances ␣NAC translocation to the nucleus and leads to its accumulation at target promoters to regulate transcription and affect bone mass.

show abstract

αNAC Requires an Interaction With c-Jun to Exert its Transcriptional Coactivation

Cited by 22 publications

References 27 publications

NACA is a positive regulator of human erythroid-cell differentiation

NACA is a positive regulator of human erythroid-cell differentiation

Sequence-Specific DNA Binding by the αNAC Coactivator Is Required for Potentiation of c-Jun-Dependent Transcription of the Osteocalcin Gene

The PTH-Gα_s-Protein Kinase A Cascade Controls αNAC Localization To Regulate Bone Mass

Contact Info

Product

Resources

About

αNAC Requires an Interaction With c-Jun to Exert its Transcriptional Coactivation

Cited by 22 publications

References 27 publications

NACA is a positive regulator of human erythroid-cell differentiation

NACA is a positive regulator of human erythroid-cell differentiation

Sequence-Specific DNA Binding by the αNAC Coactivator Is Required for Potentiation of c-Jun-Dependent Transcription of the Osteocalcin Gene

The PTH-Gαs-Protein Kinase A Cascade Controls αNAC Localization To Regulate Bone Mass

Contact Info

Product

Resources

About

The PTH-Gα_s-Protein Kinase A Cascade Controls αNAC Localization To Regulate Bone Mass