A5032626789- PARP inhibition in cancer therapy
- TGF-β signaling in diseases
- Cancer-related gene regulation
- Ubiquitin and proteasome pathways
- Epigenetics and DNA Methylation
- Kruppel-like factors research
- Immune Cell Function and Interaction
- Hedgehog Signaling Pathway Studies
- Cancer-related molecular mechanisms research
- T-cell and B-cell Immunology
- Prostate Cancer Treatment and Research
- NF-κB Signaling Pathways
- Pancreatic and Hepatic Oncology Research
- Fluorine in Organic Chemistry
- Synthesis and Reactions of Organic Compounds
- Developmental Biology and Gene Regulation
- Hippo pathway signaling and YAP/TAZ
- Synthesis and Biological Evaluation
- Cancer, Lipids, and Metabolism
- RNA modifications and cancer
- CAR-T cell therapy research
- Glioma Diagnosis and Treatment
- Fungal and yeast genetics research
- MicroRNA in disease regulation
- Protein Degradation and Inhibitors
University of Virginia
2014-2024
Oregon State University
2024
Columbia University
1996-2007
Memorial Sloan Kettering Cancer Center
1997-2005
Howard Hughes Medical Institute
1997-2005
Vall d'Hebron Hospital Universitari
2005
The Honourable Society of Lincoln's Inn
1992-1995
University of Pennsylvania
1995
St Bartholomew's Hospital
1989-1991
University of East Anglia
1989
The Saccharomyces cerevisiae Rap1 protein binds with high affinity to sites within the poly(C(1-3)A) tracts at telomeres, where it plays a role in both telomere length regulation and initiation of telomeric silencing. Rap1p initiates silencing telomeres by interacting through its carboxy-terminal domain Sir3p Sir4p, which are required for repression. This same also negatively regulates elongation, an unknown mechanism. We have identified new Rap1-interacting factor (Rif2p) that regulation....
Signal transduction by the TGF-β family involves sets of receptor serine/threonine kinases, Smad proteins that act as substrates, and Smad-associated transcription factors target specific genes. We have identified discrete structural elements dictate selective interactions between receptors Smads in BMP pathways. A cluster four residues L45 loop type I kinase domain, a matching set two L3 carboxy-terminal domain establish specificity receptor–Smad interactions. highly exposed α-helix 2...
Two phorbol ester-inducible elements (beta E2 and beta E3) within the human T-cell receptor gene enhancer each contain consensus binding sites for Ets core factor (CBF) transcription families. Recombinant Ets-1 purified CBF bound individually to E3, in which are directly adjacent. In this report, we show that bind together E3 Ets-1-CBF-DNA complexes favored over of either protein alone E2. Formation increased affinity Ets-1-DNA interactions decreased rate dissociation from DNA. were not...
TGIF is a DNA-binding homeodomain protein that has been demonstrated to play role in transforming growth factor β-regulated transcription and implicated the control of retinoid-responsive transcription. We investigated intrinsic transcriptional activity fused heterologous domain. Our results demonstrate repressor able repress from several different promoters. Repression by insensitive distance at which it bound promoter. Moreover, wild type effectively represses when its cognate site via...
TGIF (TG-interacting factor) represses transforming growth factor beta (TGF-beta)-activated gene expression and can repress transcription via a specific retinoid response element. Mutations in human are associated with holoprosencephaly, severe defect of craniofacial development both genetic environmental causes. Both TGF-beta retinoic acid signaling implicated development. Here, we analyze the role regulating responsive expression. We demonstrate that interacts ligand binding domain...
Holoprosencephaly (HPE) is a severe human genetic disease affecting craniofacial development, with an incidence of up to 1/250 conceptions and 1.3 per 10,000 live births. Mutations in the Sonic Hedgehog (SHH) gene result HPE humans mice, Shh pathway targeted by other mutations that cause HPE. However, at least 12 loci are associated humans, suggesting defects pathways contribute this disease. Although TGIF1 (TG-interacting factor) maps HPE4 locus, heterozygous loss function HPE, mouse models...
Abstract DRAIC is a 1.7 kb spliced long noncoding RNA downregulated in castration-resistant advanced prostate cancer. Decreased expression predicts poor patient outcome and seven other cancers, while increased represses growth of xenografted tumors. Here, we show that cancers with decreased have NF-κB target gene expression. downregulation cell invasion soft agar colony formation; this was dependent on activation. interacted subunits the IκB kinase (IKK) complex to inhibit their interaction...
TG-interacting factor (TGIF) is a transcriptional repressor, which represses transcription by binding directly to DNA or interacts with transforming growth β (TGFβ)-activated Smads, thereby repressing TGFβ-responsive gene expression. Mutation of TGIF in humans causes holoprosencephaly, severe genetic disorder affecting craniofacial development. Searching human expressed sequence tag data bases revealed the presence clones encoding TGIF-related protein (TGIF2), contains two regions high...
The activity of the T-cell receptor beta-chain gene enhancer is increased by activators protein kinase C pathway during activation. Analysis mutant constructs identified two elements, beta E2 and E3, conferring phorbol ester inducibility. Multimerized acted in isolation as a ester-responsive element. Both which contain consensus Ets-binding site, were shown to bind directly product c-ets-1 protooncogene. regions also bound second factor, core-binding factor. Mutation Ets site abolished...
Background Modification of proteins by the small ubiquitin like modifier (SUMO) is an essential process in mammalian cells. SUMO covalently attached to lysines target via enzymatic cascade which consists E1 and E2, activating conjugating enzymes. There also a variable requirement for non-enzymatic E3 adapter proteins, can increase efficiency specificity sumoylation process. In addition covalent attachment specific non-covalent interaction motifs (SIMs) that are generally short hydrophobic...
Rap1p is a transcriptional regulator of Saccharomyces cerevisiae, which plays roles in both activation and silencing. To identify proteins involved Rap1p-dependent regulation transcription, we used the two-hybrid system to screen for Rap1p-interacting proteins. Two clones isolated from this encode truncated protein with homology small heat shock (HSPs). Here present an analysis novel S. cerevisiae HSP, name Hsp42p. Expression HSP42 regulated by range stress conditions similar HSP26, Hsp42p...
Tgif1 and Tgif2 are transcriptional co-repressors that limit the response to TGFbeta signaling play a role in regulating retinoic-acid-mediated gene expression. Mutations human TGIF1 associated with holoprosencephaly, but it is unclear whether this result of deregulation TGFbeta/Nodal signaling, or effects on other pathways. Surprisingly, mutation mice results only relatively mild developmental phenotypes most strain backgrounds. Here, we show loss-of-function mutations both failure...
Abstract Androgen signaling through the androgen receptor (AR) directs gene expression in both normal and prostate cancer cells. regulates multiple aspects of AR life cycle, including its localization post-translational modification, but understanding how modifications are read integrated with activity has been difficult. Here, we show that ADP-ribosylation a nuclear pathway mediated by Parp7. We Parp7 mono-ADP-ribosylates agonist-bound AR, ADP-ribosyl-cysteines within N-terminal domain...