A5077633072- Developmental Biology and Gene Regulation
- TGF-β signaling in diseases
- Wnt/β-catenin signaling in development and cancer
- Epigenetics and DNA Methylation
- Congenital heart defects research
- Pluripotent Stem Cells Research
- Cancer-related gene regulation
- Kruppel-like factors research
- Cellular Mechanics and Interactions
- Connective tissue disorders research
- Hippo pathway signaling and YAP/TAZ
- Genomics and Chromatin Dynamics
- Ubiquitin and proteasome pathways
- Axon Guidance and Neuronal Signaling
- Cell Adhesion Molecules Research
- Signaling Pathways in Disease
- Connective Tissue Growth Factor Research
- Genetics, Bioinformatics, and Biomedical Research
- Lung Cancer Treatments and Mutations
- Retinoids in leukemia and cellular processes
- Coenzyme Q10 studies and effects
- Bone Metabolism and Diseases
- Microbial Natural Products and Biosynthesis
- Genetic factors in colorectal cancer
- Muscle Physiology and Disorders
University of Alabama at Birmingham
2016-2025
Marine Biological Laboratory
2021
University of Southern California
2019
Rockefeller University
1997-2003
University of Alabama
2002-2003
Institute of Genetics and Biophysics
2001
Karolinska Institutet
2001
National Cancer Institute
2001
University of California, San Francisco
2001
Smad proteins are key intracellular signaling effectors for the transforming growth factor-β superfamily of peptide factors. Following receptor-induced activation, Smads move into nucleus to activate transcription a select set target genes. The activity must be tightly regulated exert biological effects different ligands in timely manner. Here, we report identification Smurf2, new member Hect family E3 ubiquitin ligases. Smurf2 selectively interacts with receptor-regulated and preferentially...
Nodal proteins have crucial roles in mesendoderm formation and left-right patterning during vertebrate development. The molecular mechanisms of signal transduction by related ligands, however, are not fully understood. In this paper, we present biochemical functional evidence that the orphan type I serine/threonine kinase receptor ALK7 acts as a for mouse Xenopus Nodal-related 1 (Xnr1). Receptor reconstitution experiments indicate collaborates with ActRIIB to confer responsiveness Xnr1...
Intermittent administration of PTH stimulates bone formation, but the precise mechanisms responsible for responses in osteoblasts are only incompletely understood. Here we show that binding to its receptor PTH1R induced association LRP6, a coreceptor Wnt, with PTH1R. The formation ternary complex containing PTH, PTH1R, and LRP6 promoted rapid phosphorylation which resulted recruitment axin stabilization β-catenin. Activation PKA is essential PTH-induced β-catenin stabilization, not Wnt...
Transforming growth factor-β (TGF-β) and TGF-β-related factors regulate cell growth, differentiation, apoptosis, play key roles in normal development tumorigenesis. TGF-β family-induced changes gene expression are mediated by serine/threonine kinase receptors at the surface Smads as intracellular effectors. Receptor-activated combine with a common Smad4 to translocate into nucleus where they cooperate other transcription activate or repress transcription. The activities of receptor-activated...
ABSTRACT Activins and other ligands in the TGFb superfamily signal through a heteromeric complex of receptors. Disruption signaling by truncated type II activin receptor, XActRIIB (previously called XAR1), blocks mesoderm induction promotes neuralization Xenopus embryos. We report cloning characterization I XALK4. Like XActRIIB, mutant (tXALK4) formation both vitro vivo; moreover, an active form receptor induces ligand-independent manner. Unlike however, tXALK4 does not induce neural tissue....
Post-translational histone modifications play important roles in regulating gene expression programs, which turn determine cell fate and lineage commitment during development. One such modification is ubiquitination, primarily targets H2A H2B. Although ubiquitination of H2B has been generally linked to silencing activation, respectively, the functions eukaryote development are not well understood. Here, we identified USP12 USP46 as deubiquitinases that regulate Xenopus prefer nucleosomal...
Signaling through receptors of the transforming growth factor beta (TGFbeta) superfamily is mediated by cytoplasmic Smad proteins. It has been demonstrated that anchor for receptor activation (SARA) facilitates TGFbeta and activin/nodal signaling recruiting presenting Smad2/3 to complex. SARA does not bind Smad1 hence enhance bone morphogenetic protein (BMP) signaling. Here we report first time endosome-associated FYVE-domain endofin acts as a in BMP We demonstrate binds preferentially...
Neural crest cells arise from the border of neural plate and epidermal ectoderm, migrate extensively differentiate into diverse cell types during vertebrate embryogenesis. Although much has been learnt about growth factor signals gene regulatory networks that regulate development, limited information is available on how epigenetic mechanisms control this process. In study, we show Polycomb repressive complex 2 (PRC2) cooperates with transcription Snail2/Slug to modulate development in...
Vertebrate embryos undergo dramatic shape changes at gastrulation that require locally produced and anisotropically applied forces, yet how these forces are transmitted across tissues remains unclear. We show depletion of myosin regulatory light chain (RLC) levels in the embryo blocks force generation through two distinct mechanisms: destabilizing II (MII) hexameric complex inhibiting MII contractility. Molecular dissection mechanisms demonstrates normal convergence requires contractility we...
Smads, key effectors of transforming growth factor (TGF)-beta, activin, and bone morphogenetic protein (BMP) signaling, regulate gene expression interact with coactivators corepressors that modulate Smad activity. The corepressor Evi-1 exerts its oncogenic effects by repressing TGF-beta/Smad3-mediated transcription, thereby blocking TGF-beta-induced arrest. Because interacts the highly conserved MH2 domain Smad3, we investigated physical functional interaction Smad1 Smad2, downstream targets...
Abstract In Xenopus, ectodermal cell fates are determined by antagonistic interaction between the BMP subfamily of TGF-β ligands and organizer-specific secreted factors (e.g. noggin, chordin follistatin). Inhibition function these can convert cells from an epidermal to a neural fate. this study, we report that GDF6, new member Xenopus family, in with inducers. GDF6 induces epidermis inhibits tissue dissociated cells, activity is blocked presence noggin. We demonstrate binds directly inducer...
Vertebrate neural induction requires inhibition of bone morphogenetic protein (BMP) signaling in the ectoderm. However, whether BMP is sufficient to induce tissues vivo remains controversial. Here we have addressed why BMP/Smad1 does not markers efficiently Xenopus ventral ectoderm, and show that suppression both Smad1 Smad2 signals markers. Manipulations inhibit pathways, including a truncated type IIB activin receptor, Smad7 Ski, early epidermal genes ectoderm; co-expression inhibitors...
Posttranslational histone modifications play important roles in regulating chromatin-based nuclear processes. Histone H2AK119 ubiquitination (H2Aub) is a prevalent modification and has been primarily linked to gene silencing. However, the underlying mechanism remains largely obscure. Here we report identification of RSF1 (remodeling spacing factor 1), subunit RSF complex, as H2Aub binding protein, which mediates gene-silencing function this modification. associates specifically with H2Aub,...
Transforming growth factor β (TGF-β) signals regulate multiple processes during development and in adult. We recently showed that tomoregulin-1 (TMEFF1), a transmembrane protein, selectively inhibits nodal but not activin early Xenopus embryos. Here we report TMEFF1 binds to the coreceptor Cripto, does associate with either or type I ALK (activin receptor-like kinase) 4 receptor coimmunoprecipitation assays. The inhibition of signaling by ectodermal explants is rescued wild-type mutant forms...
Smad proteins are critical intracellular signaling mediators for the transforming growth factor beta (TGFbeta) superfamily. Here, we report that Erbin (for "ErbB2/Her2-interacting protein"), which contains leucine-rich repeats and a PDZ (PSD-95/DLG/ZO-1) domain, interacts specifically with Smad3 and, to lesser extent, Smad2 through novel Smad-interacting domain (SID) adjacent its domain. Increased expression of does not affect level TGFbeta-induced phosphorylation Smad2/Smad3, but it...
Cardiofaciocutaneous (CFC) syndrome is a genetic disorder characterized by distinctive facial features, congenital heart defects, and skin abnormalities. Several germline gain-of-function mutations in the RAS/RAF/MEK/ERK pathway are associated with disease, including KRAS, BRAF, MEK1 MEK2. CFC thus belongs to group of disorders known as RASopathies, which all caused pathogenic various genes encoding components RAS pathway. We recently identified novel variants YWHAZ, 14-3-3 family member,...