A5040506694- TGF-β signaling in diseases
- Pancreatic and Hepatic Oncology Research
- Bone Metabolism and Diseases
- Metabolism, Diabetes, and Cancer
- Cancer-related gene regulation
- NF-κB Signaling Pathways
- Ubiquitin and proteasome pathways
- Nutrition and Health in Aging
- Genetic factors in colorectal cancer
- Muscle Physiology and Disorders
- Pancreatic function and diabetes
- Histone Deacetylase Inhibitors Research
- Bone health and treatments
- Parathyroid Disorders and Treatments
- Cancer-related Molecular Pathways
- Protein Kinase Regulation and GTPase Signaling
- Prostate Cancer Treatment and Research
- Peptidase Inhibition and Analysis
- Acute Myeloid Leukemia Research
- Kruppel-like factors research
- Magnesium in Health and Disease
- Epigenetics and DNA Methylation
- Genetic Syndromes and Imprinting
- GDF15 and Related Biomarkers
- Connective Tissue Growth Factor Research
Virginia Commonwealth University
2019-2024
Sorbonne Université
2008-2023
Inserm
2012-2023
Centre de Recherche Saint-Antoine
1997-2023
Institute of Molecular Medicine
2023
University of Mississippi Medical Center
2014-2022
Toxicologie, Pharmacologie et Signalisation Cellulaire
2008-2021
VCU Massey Comprehensive Cancer Center
2020
Virginia Cancer Institute
2020
Children's Hospital of Richmond at VCU
2020
Transforming growth factor β (TGF-β) is a multifunctional that induces wide variety of cellular processes which affect and differentiation. TGF-β exerts its effects through heteromeric complex between two transmembrane serine/threonine kinase receptors, the type I II receptors. However, intracellular signaling pathways receptors act to generate responses remain largely undefined. Here, we report initiates cascade leading stress-activated protein kinase/c-Jun N-terminal (SAPK/JNK) activation....
Abstract BC200 is a long non-coding RNA (lncRNA) that has been implicated in the regulation of protein synthesis, yet whether dysregulation contributes to pathogenesis human diseases remains elusive. In this study, we show upregulated breast cancer; among tumor specimens there higher level estrogen receptor (ER) positive than ER-negative tumors. Further experiments activation signaling induces expression BC200. To determine significance ER-regulated expression, knockout (KO) by CRISPR/Cas9....
AKT/PKB kinases transmit insulin and growth factor signals downstream of phosphatidylinositol 3-kinase (PI3K). AKT activation involves phosphorylation at two residues, Thr(308) Ser(473), mediated by PDK1 the mammalian target rapamycin complex 2 (mTORC2), respectively. Impaired is a key in metabolic disorders involving resistance, whereas hyperactivation linked to cancer pathogenesis. Here, we identify cytoplasmic NAD(+)-dependent deacetylase, Sirt2, as novel interactor, required for optimal...
Understanding the molecular mechanisms underlying antagonistic activities of tumor necrosis factor-alpha (TNF-alpha) against transforming growth factor-beta (TGF-beta) is utmost importance given physiopathological implications these cytokines. In this report, we demonstrate that TNF-alpha prevents TGF-beta-induced Smad-specific gene transactivation without inducing detectable levels inhibitory Smad7 in human dermal fibroblasts. On other hand, c-Jun and JunB, both induced by TNF-alpha, block...
Many of the actions serine/threonine kinase receptors for transforming growth factor-β (TGFβ) are mediated by DPC4, a human MAD-related protein identified as tumor suppressor gene in pancreatic carcinoma. Overexpression DPC4 is sufficient to induce activation expression and cell cycle arrest, characteristic TGFβ response. The stress-activated kinase/c-Jun N-terminal (SAPK/JNK) also one downstream targets required TGFβ-mediated signaling. Here we report that dominant-interfering mutant...
Background Chronic hepatitis C virus (HCV) infection and associated liver cirrhosis represent a major risk factor for hepatocellular carcinoma (HCC) development. TGF-β is an important driver of fibrogenesis cancer; however, its actual impact in human cancer progression still poorly known. The aim this study was to investigate the role HCC-derived HCV core natural variants on through their signaling. Principal Findings We provide evidence that protein expression primary or mouse hepatocyte...
Transforming growth factor-β (TGF-β) regulates a wide variety of biological processes through two types Ser/Thr transmembrane receptors: the TGF-β type I receptor and II (TβRII). Upon ligand binding, activated by TβRII propagates signals to Smad proteins, which mediate activation target genes. In this study, we identify ADAM12 (a disintegrin metalloproteinase 12) as component signaling pathway that acts association with TβRII. We found functions mechanism independent its protease activity...
Runx2 is indispensable for osteoblast lineage commitment and early differentiation but also blocks maturation, thereby causing bone loss in transgenic mice. Zinc finger protein 521 (Zfp521) antagonizes vivo. Eliminating one Zfp521 allele mitigates the cleidocranial dysplasia–like phenotype of newborn Runx2+/− mice, whereas overexpressing exacerbates it. Overexpressing reverses severe osteopenia adult binds to both histone deacetylase 3 (HDAC3), promotes their association, transcriptional...
Arkadia is a RING domain E3 ubiquitin ligase that activates the transforming growth factor β (TGF-β) pathway by inducing degradation of inhibitor SnoN/Ski. Here we show contains three successive SUMO-interacting motifs (SIMs) mediate noncovalent interaction with poly-SUMO2. We identify third SIM (VVDL) to be most relevant one in this interaction. Furthermore, provide evidence can function as SUMO-targeted (STUBL) ubiquitinating SUMO chains. While SIMs are not essential for SnoN/Ski response...
Studies have shown that mesenchymal stem/stromal cells (MSCs) from bone marrow are involved in the growth and metastasis of solid tumors but mechanism remains unclear osteosarcoma (OS). Previous studies raised possibility OS may receive support associated MSCs nutrient deprived core through release supportive macromolecules factors either vesicular or non-vesicular forms. In present study, we used stressed stem (SD-MSCs), control to examine hypothesis tumor-associated provide...
Overexpression of the epigenetic modifier metastasis-associated protein 1 (MTA1) is associated with aggressive human prostate cancer. The purpose this study was to determine MTA1- targeted chemopreventive and therapeutic efficacy pterostilbene, a natural potent analog resveratrol, in pre-clinical models Here, we show that high levels MTA1 expression Pten-loss cooperate key oncogenes, including c-Myc Akt among others, promote cancer progression. Loss-of-function studies using cells indicated...
We previously reported that insulin activates nuclear factor kappaB (NF-kappaB) in Chinese hamster ovary (CHO)-R cells overexpressing wild-type receptors (IRs) through a pathway requiring IR tyrosine kinase and Raf-1 activities. now investigated whether the activation of NF-kappaB by could serve an antiapoptotic function. Insulin (10(-9)-10(-7) M) inhibited apoptosis induced serum withdrawal CHO-R concentration-dependent manner. signaling: (i) was dependent on number activity since it...
Hepatoprotection mediated by free radical scavenging molecules such as dimethyl sulfoxide (Me2SO) arose the question to whether this effect involved one or several anti-apoptotic signals. Here, using primary cultures of rat hepatocytes and in vivothioacetamide-induced liver failure, we showed that Me2SO failed prevent any cleavage initiator caspase-8 -9 but constantly inhibited procaspase-3 maturation apoptosis execution, pointing an efficient inhibition cleaved caspase activities. Evidence...
Smad proteins are central mediators of the transcriptional effects transforming growth factor β (TGF-β) superfamily that regulate a wide variety biological processes. Smad7, an inhibitory protein prevents TGF-β signaling by interacting with activated type I receptor, was recently shown to induce sensitization cells different forms cell death. Here we examined effect Smad7 on c-Jun N-terminal kinase (JNK) cascade and investigated role this in both apoptotic functions Smad7. The transient...