Anastasia M Jacko

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Transforming growth factor β-1 (TGFβ-1)-induced phosphorylation of transcription factors Smad2 and Smad3 plays a crucial role in the pathogenesis of idiopathic pulmonary fibrosis (IPF). However, the molecular regulation of Smad2/Smad3 proteins stability remains a mystery. Here, we show that ubiquitin carboxyl-terminal hydrolase-L5 (UCHL5 or UCH37)(More)
Lysophosphatidic acid (LPA) is a bioactive lipid mediator of inflammation via the LPA receptors 1-6. We and others have previously described proinflammatory and profibrotic activities of LPA signaling in bleomycin- or lipopolysaccharide (LPS)-induced pulmonary fibrosis or lung injury models. In this study, we investigated if LPA signaling plays a role in(More)
Glycogen synthase kinase-3β (GSK3β) has diverse biological roles including effects on cellular differentiation, migration, and inflammation. GSK3β phosphorylates proteins to generate phosphodegrons necessary for recognition by Skp1/Cullin-1/F-box (SCF) E3 ubiquitin ligases leading to subsequent proteasomal degradation of these substrates. However, little is(More)
Cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB)-binding protein (CBP) is a histone acetyltransferase that plays a pivotal role in the control of histone modification and the expression of cytokine-encoding genes in inflammatory diseases, including sepsis and lung injury. We found that the E3 ubiquitin ligase subunit FBXL19(More)
Lysophosphatidic acid receptor 1 (LPA1) is a druggable target for treating pulmonary inflammatory diseases. However, the molecular regulation of LPA1 stability, a factor that critically impacts its biological activity, remains largely unknown. Here we identify two enzymes that regulate the balance of LPA1 ubiquitination and deubiquitination. Ubiquitin E3(More)
Lysophosphatidic acid (LPA) is a bioactive lysophospholipid, which plays a crucial role in the regulation of cell proliferation, migration, and differentiation. LPA exerts its biological effects mainly through binding to cell-surface LPA receptors (LPA1-6), which belong to the G protein-coupled receptor (GPCR) family. Recent studies suggest that cross-talk(More)
The transforming growth factor β-1 (TGFβ-1) signaling pathway plays a central role in the pathogenesis of pulmonary fibrosis. Two TGFβ-1 receptors, TβRI and TβRII, mediate this pathway. TβRI protein stability, as mediated by the ubiquitin/de-ubiquitination system, has been well studied; however, the molecular regulation of TβRII still remains unclear. Here(More)
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