ArticleThe Biochemical journal2012
SP-1 regulation of MMP-9 expression requires Ser586 in the PEST domain.
Article in The Biochemical journal, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 36 citations in OpenAlex.
- Identification of gene regulatory networks affected across drug-resistant epilepsies.Nature communications · 2024Article
- The usefulness of MMP-9, TIMP-1 and MMP-9/TIMP-1 ratio for diagnosis and assessment of COPD severity.European journal of medical research · 2023Observational
- Lack of GD3 synthase (St8sia1) attenuates malignant properties of gliomas in genetically engineered mouse model.Cancer science · 2021Article
- Metalloproteinases in Ovarian Cancer.International journal of molecular sciences · 2021Review
- Endothelin-1 Upregulates Activin Receptor-Like Kinase-1 Expression via GFrontiers in cardiovascular medicine · 2021Article
- Ezrin mediates both HGF/Met autocrine and non-autocrine signaling-induced metastasis in melanoma.International journal of cancer · 2018Article
- Sirtuin 6 contributes to migration and invasion of osteosarcoma cells via the ERK1/2/MMP9 pathway.FEBS open bio · 2017Article
- Down regulation of human positive coactivator 4 suppress tumorigenesis and lung metastasis of osteosarcoma.Oncotarget · 2017Article
- Miconazole protects blood vessels from MMP9-dependent rupture and hemorrhage.Disease models & mechanisms · 2017Article
- Lysophosphatidic Acid Is Associated with Atherosclerotic Plaque Instability by Regulating NF-κB Dependent Matrix Metalloproteinase-9 Expression via LPAFrontiers in physiology · 2017Article
- Fisetin inhibits epidermal growth factor-induced migration of ARPE-19 cells by suppression of AKT activation and Sp1-dependent MMP-9 expression.Molecular vision · 2017Article
- MMP-9 signaling in the left ventricle following myocardial infarction.American journal of physiology. Heart and circulatory physiology · 2016Review
- Article
- SP1 and UTE1 Decoy ODNs inhibit activation and proliferation of hepatic stellate cells by targeting tissue inhibitors of metalloproteinase 1.Cell & bioscience · 2016Article
- Matrix metalloproteinases as therapeutic targets for idiopathic pulmonary fibrosis.American journal of respiratory cell and molecular biology · 2015Review
- Article
- Differential regulation of MMPs by E2F1, Sp1 and NF-kappa B controls the small cell lung cancer invasive phenotype.BMC cancer · 2014Article
- CXCL12 induces connective tissue growth factor expression in human lung fibroblasts through the Rac1/ERK, JNK, and AP-1 pathways.PloS one · 2014Article
- Matrix metalloproteinase-9: Many shades of function in cardiovascular disease.Physiology (Bethesda, Md.) · 2013Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Rac1, a small GTPase, regulates macrophage MMP (matrix metalloproteinase)-9 in an ERK (extracellular-signal-regulated kinase)- and SP (specificity protein)-1-dependent manner. SP-1 contains a PEST (Pro-Glu-Ser-Thr) domain that may modulate protein stability. We hypothesize that Thr578, Ser586 and/or Ser587 in the PEST domain are required for SP-1 stability and MMP-9 expression secondary to activation of ERK, a serine/threonine kinase. We determined the effects of Rac1 and ERK on MMP-9 expression driven by SP-1WT (wild-type) and the SP-1 mutants T578A, S586A and S587A. Expression of WT and mutant SP-1 increased MMP9 promoter activity in alveolar macrophages. However, constitutively active Rac1 suppressed MMP9 promoter activity in cells expressing SP-1WT, SP-1T578A and SP-1S587A, but not SP-1S586A. Furthermore, constitutive ERK activation, which was inhibited by Rac1, significantly increased MMP9 transcription in cells expressing SP-1WT, but not SP-1S586A. As Rac1 activation and ERK inactivation increased degradation of SP-1WT and not SP-1S586A, the results of the present study suggest that SP-1 stability mediated at Ser586 regulates MMP9 transcription. Ex vivo, alveolar macrophages obtained from patients with asbestosis had less MMP-9 expression that was associated with decreased SP-1 expression and ERK activation. These observations demonstrate that Ser586 in the PEST domain of SP-1 is important for MMP9 gene expression in alveolar macrophages and highlight the importance of these proteins in pulmonary fibrosis.
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Registered trials
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