Activation of Transcription Factor SAF Involves Its Phosphorylation by Protein Kinase C

Ray, Alpana; Fields, Alan P.; Ray, Bimal K.

doi:10.1074/jbc.m007907200

Cited by 25 publications

(23 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The SAF family of transcription factors was initially identified as a regulator of serum amyloid A, an inflammation-responsive gene. The DNA binding activity of SAF-1 is normally detected in many tissues, but many inflammatory agents, including IL-1 and IL-6 alone or in combination (29), PMA (30), and bacterial lipopolysaccharide (25), are known to increase its DNA binding activity and overall transactivation potential. Phosphorylation of SAF-1 by protein kinase is critical for its action.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Induction of matrix metalloproteinase 1 gene expression is regulated by inflammation‐responsive transcription factor SAF‐1 in osteoarthritis

Ray¹,

Kuroki²,

Cook³

et al. 2003

Arthritis & Rheumatism

Self Cite

View full text Add to dashboard Cite

Objective. To identify specific transcription factors that are activated in the cartilage tissue of osteoarthritis (OA) patients and are involved in the expression of matrix metalloproteinase 1 (MMP-1).Methods. DNase I footprint and electrophoretic mobility shift assays were performed to identify active elements of the MMP1 promoter and the transcription factors that interact with it. The relative abundance of the involved transcription factor in the cartilage was determined by immunohistochemical analysis. The role of serum amyloid A-activating factor 1 (SAF-1) in MMP-1 expression was assessed by transient transfection assay with plasmids containing either a functional or an antisense SAF-1 complementary DNA.Results. A novel promoter element was detected in the human MMP1 gene, and the inflammationresponsive transcription factor SAF-1 was found to interact with it. SAF-1 activity was detected in the chondrocytes of OA cartilage, where most of the cells stained positive for SAF-1. Overexpression of SAF-1 in OA chondrocytes increased the expression of the MMP1 promoter, and interference of endogenous SAF-1 activity by antisense SAF-1 messenger RNA inhibited interleukin-1-mediated MMP1 promoter activity.Conclusion. The results indicate that SAF-1 is involved in the regulation of MMP1 gene expression and it is highly abundant in the articular cartilage chondrocytes of OA patients. The data also demonstrate that control of SAF-1 activity can suppress induced expression of MMP-1. Conceivably, SAF-1 could be a potential therapeutic target to control the overexpression of MMP-1 associated with the pathogenesis of OA.

show abstract

Section: Discussionmentioning

confidence: 99%

“…Cytokine-responsive induction of SAF-1 activity is mediated by the mitogen-activated protein kinase (MAPK) signaling pathway (31). The PMAmediated induction of SAF-1 involves its phosphorylation by protein kinase C␤ (30). Protein kinase A has also been shown to phosphorylate and activate SAF-1 (32,33).…”

Section: Discussionmentioning

confidence: 99%

Induction of matrix metalloproteinase 1 gene expression is regulated by inflammation‐responsive transcription factor SAF‐1 in osteoarthritis

Ray¹,

Kuroki²,

Cook³

et al. 2003

Arthritis & Rheumatism

Self Cite

View full text Add to dashboard Cite

show abstract

“…It is loosely associated with the mitochondrial membrane in normal cells, but integrates into mitochondrial membranes during induction of cell death. 47 Overexpression of BNIP3 results in a caspaseindependent cell death with features of necrosis, including opening of the permeability transition pore, and evidence of mitochondrial autophagy. 48 Hspin is a transmembrane protein that is localized primarily in the mitochondria.…”

Section: Inhibition Of Apoptosis Upstream Of the Mitochondria Preventmentioning

confidence: 99%

Macroautophagy versus mitochondrial autophagy: a question of fate?

Kundu

Thompson²

2005

Cell Death Differ

107

View full text Add to dashboard Cite

Autophagy is a catabolic process that allows recycling of cytoplasmic components (including organelles) into basic components, offering a bioenergetically efficient alternative to de novo synthesis. In yeast, autophagy functions primarily as an adaptive mechanism allowing survival in the response to changes in the availability of nutrients in the environment. Over the past decade, genetic screens performed in yeast have elucidated many of the molecular components involved in this adaptive response. [1][2][3] More recently, the roles of homologous genes are being explored in multicellular organisms and in cells derived from these organisms. 4 These studies have demonstrated that while autophagy is often induced as part of an adaptive response, induction of autophagy may also lead to cell death. During Drosophila larval development, for example, starvation-induced autophagy occurs in the larval fat body and is required for maintaining circulating nutrient levels and survival of the larvae under unfavorable nutritional conditions; 5 by contrast, programmed autophagy results in cell death and is the primary means of removing certain larval organs during metamorphosis. 6 On a cellular level, autophagy is observed prior to apoptosis in growth factor-deprived neuronal cultures. 7,8 In cells lacking critical proapoptotic proteins, the adaptive process of autophagy aimed at maintaining bioenergetic homeostasis can be unmasked in response to growthfactor withdrawal. 9 In contrast, cell death in response to a variety of chemicals has been suggested to result from autophagic destruction of the cell and to be suppressed by inhibition of autophagy. 10 The factors that determine whether induction of autophagy contributes to cell survival or cell death are not well-elucidated; however, two key issues may be the rate of autophagic degradation and the specificity of the engulfed components. Although autophagy is generally considered a nonspecific process, there are instances where the mitochondria (and other organelles) appear to be specifically targeted. Here, we focus on the signals and pathways involved in regulating the induction of autophagy and mitochondrial autophagy in yeast and how these processes are relevant to survival and death of mammalian cells.In general terms, 'autophagy' refers to any intracellular process that involves the degradation of cytosolic components by the lysosome. There are at least three distinct autophagic pathways: macroautophagy, microautophagy and chaperone-mediated autophagy. Macroautophagy is a multistep process by which portions of cytoplasm and/or organelles are sequestered in a double or multimembrane structure ('autophagosome') and delivered to the lysosome for degradation (Figure 1). Upon fusion of the autophagosome with the lysosome, it becomes an autophagolysosome or autophagic vacuole. Although macroautophagy is generally considered a nonspecific process there are instances in which organelles, such as mitochondria and peroxisomes, appear to be preferentially sequestered. These process...

show abstract

“…SAF-1 DNA-binding activity is normally detected in many tissues at a low level, but many inflammatory agents, including lipopolysaccharide (48), IL-1, IL-6 (45), and minimally modified low-density lipoprotein (46), are known to increase its DNA-binding activity and overall transactivating potential. In a recent study, we have shown that protein kinase C ␤ regulates phorbol 12-myristate 13-acetate-mediated activation of SAF-1 (39). As different inflammatory agents are known to activate different signaling pathways, it is likely that an additional protein kinase(s) is involved in the regulation of SAF activity in response to diverse inflammatory agents.…”

mentioning

confidence: 99%

Cytokine-Responsive Induction of SAF-1 Activity Is Mediated by a Mitogen-Activated Protein Kinase Signaling Pathway

Ray

2002

Molecular and Cellular Biology

Self Cite

View full text Add to dashboard Cite

SAF-1, a zinc finger transcription factor, is activated by a number of inflammatory agents, including interleukin-1 (IL-1) and IL-6. It is involved in the cytokine-mediated transcriptional induction of serum amyloid A, an acute-phase plasma protein that is associated with the pathogenesis of reactive amyloidosis, rheumatoid arthritis, and atherosclerosis. Here, we show that the mitogen-activated protein (MAP) kinase signaling pathway regulates cytokine-mediated induction of the DNA-binding activity and transactivation potential of SAF-1. Phosphorylation of endogenous SAF-1 in response to IL-1 and IL-6 was markedly inhibited by the addition of MAP kinase inhibitors. Consistent with this finding, we show that a consensus MAP kinase phosphorylation site, PPTP, within SAF-1 could be phosphorylated by MAP kinase in vitro. To analyze the contribution of MAP kinase in the activation of SAF-1, we prepared two independent mutant proteins in which the threonine residue of the PPTP motif was altered to either valine or alanine. These mutant proteins lost the ability to be phosphorylated by MAP kinase both in vivo and in vitro and exhibited a significantly reduced ability to promote expression of the SAF-1-regulated promoter. While the DNA-binding activity of wild-type SAF-1 protein was markedly increased upon phosphorylation with MAP kinase, no such increase could be detected with the mutant SAF-1 proteins. Further analysis with the GAL-4 reporter system showed that mutation of the MAP kinase phosphorylation site considerably lowers the transactivation potential of SAF-1. Together, these results show that activation of SAF-1 in response to IL-1 and -6 is mediated via MAP kinase-regulated phosphorylation.

show abstract

Activation of Transcription Factor SAF Involves Its Phosphorylation by Protein Kinase C

Cited by 25 publications

References 31 publications

Induction of matrix metalloproteinase 1 gene expression is regulated by inflammation‐responsive transcription factor SAF‐1 in osteoarthritis

Induction of matrix metalloproteinase 1 gene expression is regulated by inflammation‐responsive transcription factor SAF‐1 in osteoarthritis

Macroautophagy versus mitochondrial autophagy: a question of fate?

Cytokine-Responsive Induction of SAF-1 Activity Is Mediated by a Mitogen-Activated Protein Kinase Signaling Pathway

Contact Info

Product

Resources

About