Human Prolyl-4-hydroxylase α(I) Transcription Is Mediated by Upstream Stimulatory Factors

Chen, Li; Shen, Ying H.; Wang, Xinwen; Wang, Jing; Gan, Ye‐Hua; Chen, Nanyue; Wang, Jian; LeMaire, Scott A.; Coselli, Joseph S.; Wang, Xing Li

doi:10.1074/jbc.m511237200

Cited by 42 publications

(37 citation statements)

References 58 publications

(51 reference statements)

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“…15,16 Previously, we have reported that an E-box-like sequence (CACGGG) located at Ϫ135bp of the P4H␣1 promoter is responsible for 80% of the basal transcriptional activity and appears to be upregulated by TGF␤1 and downregulated by cigarette smoking. 17 In the current study, we investigated the effects of TNF-␣ on P4H␣1 expression and the underlying molecular mechanisms of these effects. We have found that TNF-␣1 suppresses P4H␣1 expression at the transcriptional level.…”

Section: See Page 1677mentioning

confidence: 99%

“…The details of the primers and sequence confirmation of these plasmids have been described previously. 17 To define the nucleotides within the region Ϫ32 to ϩ18bp in the P4H␣1 promoter responsible for the binding of TNF-␣ responsive protein NonO, we constructed P4H␣1 promoter pGL3 reporter with serial deletions of Ϫ32 to Ϫ15bp, Ϫ32 to Ϫ3bp. The primers of the region Ϫ15pGL3 vector were sense: GGTAC-CACGGGCTCCCTCTGCTGC CCAG, antisense: GCTAGCAC-CACCACAGCGGGAAGGAATGG.…”

Section: Plasmid Constructionmentioning

confidence: 99%

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TNF-α Suppresses Prolyl-4-Hydroxylase α1 Expression via the ASK1–JNK–NonO Pathway

Zhang

Shen

et al. 2007

ATVB

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Background-Inflammation is known to contribute to the pathogenesis of vascular diseases in which arterial wall extracellular matrix (ECM) homeostasis is disrupted. Tumor necrosis factor-␣ (TNF-␣), a pivotal cytokine that regulates ECM metabolism by increasing degradation and decreasing production of arterial collagens, is associated with vulnerable plaques and aortic aneurysms. Methods and Results-In the current study, we showed that, when administered in doses of 1 to 100 ng/mL, TNF-␣ dose-dependently downregulated the expression of prolyl-4-hydroxylase ␣I [P4H␣(I)]-the rate-limiting subunit for the P4H enzyme essential for procollagen hydroxylation, secretion, and deposition in primary human aortic smooth muscle cells (HASMCs). Using a progressive deletion cloning approach, we characterized the TNF-␣-responsive element (TaRE) in the human P4H␣(I) promoter and found that a negative regulatory region at the position of Ϫ32 to ϩ18bp is responsible for Ϸ80% of TNF-␣-mediated suppression. Using oligonucleotide-based transcription factor pull-down method in which proteins were resolved in 1-D gel electrophoresis and identified using LC-MS/MS, we identified the NonO protein binds this region. When NonO expression silenced with specific siRNA, we found that 70% of the TNF-␣-mediated P4H␣ suppression was abolished, which appeared to be mediated by the ASK1-JNK pathway. Conclusions-Our findings define a novel molecular pathway for inflammation associated extracellular matrix dysregulation, which may account for atherosclerotic plaque rupture and aortic aneurysm formation. Further understanding of this pathway may facilitate development of novel therapeutics for vascular diseases. (Arterioscler Thromb Vasc Biol.

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Section: See Page 1677mentioning

confidence: 99%

Section: Plasmid Constructionmentioning

confidence: 99%

TNF-α Suppresses Prolyl-4-Hydroxylase α1 Expression via the ASK1–JNK–NonO Pathway

Zhang

Shen

et al. 2007

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“…Based on the enhanceosome concept, we hypothesized that another transcription factor(s) is required to activate HIF target genes during hypoxia. We found that many HIF target genes, including HMOX1 (41,42,63,64,84,88,89,112), SFTPA1 (13,32,33), CXCR4 (73,90,96), PAI1 (2,18,27,29,47,57,58,66), BDNF (48,97), hTERT (3,9,35,44,52,61,67,72,75,110,113), CTSB (111) (107), and P4H␣(I) (10,43,98), are also reported to be activated by the transcription factor upstream stimulatory factor 1 (USF1) or USF2, suggesting a possible role of USF1/USF2 in the hypoxic response.USFs (USF1 and USF2) are basic helix-loop-helix-leucine zipper (bHLH-LZ) transcription factors that are expressed ubiquitously, albeit at different levels depending on the tissue type (14,36,94,95,101 (7,8,19) as either USF1/USF1 or USF2/USF2 homodimers or USF1/USF2 heterodimers. The major functional USF complexes in most cell types are USF1/USF2 heterodimers (94, 101).…”

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confidence: 99%

Upstream Stimulatory Factor 2 and Hypoxia-Inducible Factor 2α (HIF2α) Cooperatively Activate HIF2 Target Genes during Hypoxia

Pawlus

Wang

Ware

et al. 2012

Molecular and Cellular Biology

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While the functions of hypoxia-inducible factor 1␣ (HIF1␣)/aryl hydrocarbon receptor nuclear translocator (ARNT) and HIF2␣/ARNT (HIF2) proteins in activating hypoxia-inducible genes are well established, the role of other transcription factors in the hypoxic transcriptional response is less clear. We report here for the first time that the basic helix-loop-helix-leucine-zip transcription factor upstream stimulatory factor 2 (USF2) is required for the hypoxic transcriptional response, specifically, for hypoxic activation of HIF2 target genes. We show that inhibiting USF2 activity greatly reduces hypoxic induction of HIF2 target genes in cell lines that have USF2 activity, while inducing USF2 activity in cells lacking USF2 activity restores hypoxic induction of HIF2 target genes. Mechanistically, USF2 activates HIF2 target genes by binding to HIF2 target gene promoters, interacting with HIF2␣ protein, and recruiting coactivators CBP and p300 to form enhanceosome complexes that contain HIF2␣, USF2, CBP, p300, and RNA polymerase II on HIF2 target gene promoters. Functionally, the effect of USF2 knockdown on proliferation, motility, and clonogenic survival of HIF2-dependent tumor cells in vitro is phenocopied by HIF2␣ knockdown, indicating that USF2 works with HIF2 to activate HIF2 target genes and to drive HIF2-depedent tumorigenesis.A hypoxic microenvironment is frequently found in solid tumors. The transcriptional response mediated by hypoxia-inducible factor 1␣ (HIF1␣)/aryl hydrocarbon receptor nuclear translocator (ARNT) (HIF1) and HIF2␣/ARNT (HIF2) plays a critical role in malignant progression by increasing expression of genes involved in angiogenesis, anaerobic metabolism, and other processes that enable tumor cells to survive and/or escape their O 2 -deficient microenvironment (25,53,56,93).It is well established that multiple transcription factors (TFs) are required to achieve maximal activation of target genes in response to a specific stimulus. This multifactorial transcription complex has been termed the "enhanceosome" (100). Individual factors in the enhanceosome complex may promote transcription initiation by recruiting RNA polymerase II (Pol II)/general transcription factors and/or recruiting chromatin-modifying enzymes, such as histone acetylases and chromatin remodeling complexes. In addition, TFs such as Myc increase gene expression by recruiting elongation factors to regulate Pol II pause release (77). Thus, reduced levels of transcription could occur in the absence of factors that have redundant functions within the enhanceosome, while other transcription factors having unique functions are absolutely required for gene activation.The role of HIF1 and HIF2 in activating hypoxia-inducible genes is well established (21,37,48,79,103). However, the other transcription factors required for hypoxic activation of HIF target genes have been much less studied. Based on the enhanceosome concept, we hypothesized that another transcription factor(s) is required to activate HIF target genes during hypoxia. We ...

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“…It can form homo-and heterodimers and recognize in vitro a CACGTG core sequence termed E box (31). Through binding to E boxes of target genes, USF2 has been demonstrated to regulate expression of many genes (4,9,10,13,17,22,23,34,39). In our previous studies, we demonstrated that high-glucose exposure stimulated nuclear USF2 accumulation, which mediated high-glucose conditions and induced TSP1 gene expression and TGF-␤ activity in glomerular mesangial cells, suggesting a role of USF2 in the development of diabetic renal complications.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of upstream stimulatory factor 2 accelerates diabetic kidney injury

Liu¹,

Shi²,

Wang³

2007

American Journal of Physiology-Renal Physiology

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Liu S, Shi L, Wang S. Overexpression of upstream stimulatory factor 2 accelerates diabetic kidney injury. Am J Physiol Renal Physiol 293: F1727-F1735, 2007. First published September 19, 2007; doi:10.1152/ajprenal.00316.2007.-Diabetic nephropathy is the most common cause of end-stage renal failure in the United States. Hyperglycemia is an important factor in the pathogenesis of diabetic nephropathy. Hyperglycemia upregulates the expression of transforming growth factor-␤ (TGF-␤), which stimulates extracellular matrix deposition in the kidney, contributing to the development of diabetic nephropathy. Our previous studies demonstrated that the transcription factor, upstream stimulatory factor 2 (USF2), was upregulated by high glucose, which bound to an 18-bp sequence in the thrombospondin 1 (TSP1) gene promoter and regulated high glucose-induced TSP1 expression and TGF-␤ activity in mesangial cells, suggesting that USF2 might play a role in the development of diabetic nephropathy.In the present studies, we examined the effect of overexpression of USF2 on the development of diabetic nephropathy. Type 1 diabetes was induced in USF2 transgenic mice [USF2 (Tg)] and their wild-type littermates (WT) by injection of streptozotocin. Four groups of mice were studied: control WT, control USF2 (Tg), diabetic WT, and diabetic USF2 (Tg). Mice were killed after 15 wk of diabetes onset. At the end of studies, control USF2 (Tg) mice (ϳ6 mo old) exhibited increased urinary albumin excretion. These mice also exhibited glomerular hypertrophy, accompanied by increased TSP1, active TGF-␤, fibronectin accumulation in the glomeruli compared with control WT littermates. Type 1 diabetes onset further augmented the urinary albumin excretion and glomerular hypertrophy in the USF2 (Tg) mice. These findings suggest that overexpression of USF2 accelerates the development of diabetic nephropathy. TGF-␤DIABETIC NEPHROPATHY is the most common cause of end-stage renal failure in the United States. About 20 -30% of type 1 and type 2 diabetic patients develop diabetic nephropathy (5). Diabetic nephropathy is characterized by both glomeruosclerosis with thickening of the glomerular basement membrane and mesangial matrix expansion, and tubulointerstitial fibrosis (11). Hyperglycemia is an important factor in the pathogenesis of diabetic nephropathy (32). Hyperglycemia upregulates the expression of a fibrogenic growth factor, transforming growth factor-␤ (TGF-␤), contributing to the development of diabetic nephropathy (29). The importance of TGF-␤ in the development of diabetic nephropathy is well-established. TGF-␤ is involved in both the early and later stages of diabetic nephropathy (3,20,27). Moreover, studies have shown that anti-TGF-␤ antibodies prevent the development of diabetic nephropathy (2, 28), providing a direct evidence for the involvement of TGF-␤ in the pathogenesis of diabetic nephropathy. The fibrogenic effects of TGF-␤ are due to its upregulation of extracellular matrix components, including collagen, fibronectin, osteopontin, and ...

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Human Prolyl-4-hydroxylase α(I) Transcription Is Mediated by Upstream Stimulatory Factors

Cited by 42 publications

References 58 publications

TNF-α Suppresses Prolyl-4-Hydroxylase α1 Expression via the ASK1–JNK–NonO Pathway

TNF-α Suppresses Prolyl-4-Hydroxylase α1 Expression via the ASK1–JNK–NonO Pathway

Upstream Stimulatory Factor 2 and Hypoxia-Inducible Factor 2α (HIF2α) Cooperatively Activate HIF2 Target Genes during Hypoxia

Overexpression of upstream stimulatory factor 2 accelerates diabetic kidney injury

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