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Olmsted syndrome (OS) is a rare congenital disorder characterized by palmoplantar and periorificial keratoderma, alopecia in most cases, and severe itching. The genetic basis for OS remained unidentified. Using whole-exome sequencing of case-parents trios, we have identified a de novo missense mutation in TRPV3 that produces p.Gly573Ser in an individual(More)
The cascade of phosphorylation is a pivotal event in transforming growth factor beta (TGFbeta) signaling. Reversible phosphorylation regulates fundamental aspects of cell activity. TGFbeta-induced Smad7 binds to type I receptor (TGFbeta type I receptor; TbetaRI) functioning as a receptor kinase antagonist. We found Smad7 interacts with growth arrest and DNA(More)
Bone marrow mesenchymal stem cells (BMSCs) exhibit an age-dependent reduction in osteogenesis that is accompanied by an increased propensity toward adipocyte differentiation. This switch increases adipocyte numbers and decreases the number of osteoblasts, contributing to age-related bone loss. Here, we found that the level of microRNA-188 (miR-188) is(More)
Inhibitory Smads (I-Smads), including Smad6 and Smad7, were initially characterized as cytoplasmic antagonists in the transforming growth factor-beta signaling pathway. However, I-Smads are also localized in the nucleus. Previously, we have shown that Smad6 can function as a transcriptional co-repressor. In this study, we found both Smad6 and Smad7 interact(More)
Bone morphogenetic proteins (BMPs) are multi-functional growth factors that belong to the transforming growth factor beta (TGFbeta) superfamily. The roles of BMPs in embryonic development and cellular functions in postnatal and adult animals have been extensively studied in recent years. Signal transduction studies have revealed that Smads 1, 5 and 8 are(More)
Smad4 is a key intracellular mediator for the transforming growth factor-beta (TGF-beta) superfamily of growth factors and is also an important tumor suppressor. The receptor-regulated Smad (R-Smad) proteins are regulated by ubiquitin-mediated degradation, yet the precise control of Smad4 protein stability is unclear. We have identified SCF(beta-TrCP1), a(More)
Parathyroid hormone (PTH) regulates calcium homeostasis and bone metabolism by activating PTH type I receptor (PTH1R). Here we show that transforming growth factor (TGF)-beta type II receptor (TbetaRII) forms an endocytic complex with PTH1R in response to PTH and regulates signalling by PTH and TGF-beta. TbetaRII directly phosphorylates the PTH1R(More)
To better understand the potential use of fetal marrow stromal cells (MSCs) in bone tissue engineering, we compared the ability of these cells with those of adult MSCs with respect to osteoblasts differentiation in the presence or absence of glucocorticoids. Cells were grown for 3-4 weeks in basal medium or supplemented with 100 nM dexamethasone (DEX, a(More)
Neuroprotection has been the focus of several current efforts to develop a strategy for the treatment of Parkinson's disease (PD). The B-type monoamine oxidase (MAO-B) inhibitor deprenyl (selegiline) is used clinically as a PD therapeutic agent, however, its cytoprotective mechanism has not yet been fully elucidated. In this study, we show that deprenyl(More)
Smad4, also known as deleted in pancreatic carcinoma locus 4 (DPC4), is a critical co-factor in signal transduction pathways activated by transforming growth factor (TGF)-beta-related ligands that regulate cell growth and differentiation. Mutations in Smad4/DPC4 have been identified in approximately 50% of pancreatic adenocarcinomas. Here we report that(More)