A5081360002- Ubiquitin and proteasome pathways
- Protein Degradation and Inhibitors
- Cell Adhesion Molecules Research
- Cancer-related Molecular Pathways
- Cellular Mechanics and Interactions
- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- Peptidase Inhibition and Analysis
- Cancer, Hypoxia, and Metabolism
- Microtubule and mitosis dynamics
- Enzyme Structure and Function
- Histone Deacetylase Inhibitors Research
- Viral-associated cancers and disorders
- 14-3-3 protein interactions
- Glycosylation and Glycoproteins Research
- Cytomegalovirus and herpesvirus research
- DNA Repair Mechanisms
- Cellular transport and secretion
- Hippo pathway signaling and YAP/TAZ
- Protein Kinase Regulation and GTPase Signaling
- Mitochondrial Function and Pathology
- Metabolism, Diabetes, and Cancer
- Biochemical and Molecular Research
- Endoplasmic Reticulum Stress and Disease
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
Mount Sinai Hospital
2011-2024
Lunenfeld-Tanenbaum Research Institute
2012-2024
Sinai Health System
2018-2024
Mount Sinai Hospital
2008-2011
Dana-Farber Cancer Institute
2004-2008
Harvard University
2004-2008
University of Toronto
2007
McMaster University
1994-2000
Health Sciences Centre
1994
While the antibody response to SARS-CoV-2 has been extensively studied in blood, relatively little is known about saliva and its relationship systemic levels. Here, we profiled by enzyme-linked immunosorbent assays (ELISAs) IgG, IgA IgM responses spike protein (full length trimer) receptor-binding domain (RBD) serum of acute convalescent patients with laboratory-diagnosed COVID-19 ranging from 3-115 days post-symptom onset (PSO), compared negative controls. Anti-SARS-CoV-2 were readily...
Focal adhesion kinase (FAK) is an essential that regulates developmental processes and functions in the pathology of human disease.An intramolecular autoinhibitory interaction between FERM catalytic domains a major mechanism regulation.Based upon structural studies, fluorescence resonance energy transfer (FRET)-based FAK biosensor discriminates autoinhibited active conformations was developed.This used to probe conformational change live cells regulation.The demonstrates directly undergoes...
Cerebral cavernous malformations (CCMs) are alterations in brain capillary architecture that can result neurological deficits, seizures, or stroke. We recently demonstrated CCM3, a protein mutated familial CCMs, resides predominantly within the STRIPAK complex (striatin interacting phosphatase and kinase). Along with contains Ser/Thr PP2A. The PP2A holoenzyme consists of core catalytic subunit along variable scaffolding regulatory subunits. Within STRIPAK, striatin family members act as also...
ABSTRACT The replication and stable maintenance of latent Epstein-Barr virus (EBV) DNA episomes in human cells requires only one viral protein, nuclear antigen 1 (EBNA1). To gain insight into the mechanisms by which EBNA1 functions, we used a yeast two-hybrid screen to detect proteins that interact with EBNA1. We describe here isolation EBP2 (EBNA1 binding protein 2), specifically interacts was also shown bind DNA-bound one-hybrid system, EBP2-EBNA1 interaction confirmed...
Focal adhesion kinase (FAK) is a non-receptor tyrosine that localizes to focal adhesions in adherent cells. Through phosphorylation of proteins assembled at the cytoplasmic tails integrins, FAK promotes signaling events modulate cellular growth, survival, and migration. The amino-terminal region contains sequence homology with band 4.1 ezrin/radixin/moesin (ERM) termed FERM domain. domains are found variety cytoskeletal thought mediate intermolecular interactions partner phospholipids plasma...
Pleckstrin homology (PH) domains are phosphoinositide (PI)-binding modules that target proteins to membrane surfaces. Here we define a family of PH domain proteins, including Tiam1 and ArhGAP9, demonstrates specificity for PI(4,5)P2, as well PI(3,4,5)P3 PI(3,4)P2, the products PI 3-kinase. These members utilize non-canonical binding pocket related employed by β-spectrin. Crystal structures ArhGAP9 in complex with headgroups Ins(1,3,4)P3, Ins(1,4,5)P3, Ins(1,3,5)P3 reveal how two adjacent...
Abstract While the antibody response to SARS-CoV-2 has been extensively studied in blood, relatively little is known about mucosal immune and its relationship systemic levels. Since initially replicates upper airway, oral cavity likely an important parameter that influences course of infection, but how it correlates serum not known. Here, we profile by enzyme linked immunosorbent assays (ELISAs) IgG, IgA IgM responses spike protein (full length trimer) receptor binding domain (RBD) (n=496)...
Targeted protein degradation (TPD) strategies exploit bivalent small molecules to bridge substrate proteins an E3 ubiquitin ligase induce degradation. Few E3s have been explored as effectors due a dearth of E3-binding molecules. We show that genetically induced recruitment the GID4 subunit CTLH complex induces An NMR-based fragment screen followed by structure-guided analog elaboration identified two binders GID4, 16 and 67, with Kd values 110 17 μM in vitro. A parallel DNA-encoded library...
From the results of deletion analyses, FERM domain FAK has been proposed to inhibit enzymatic activity and repress signaling. We have identified a sequence in that is important for signaling vivo. Point mutations this had little effect upon catalytic vitro. However, mutant exhibits reduced tyrosine phosphorylation dramatically Src family kinase binding. Further, abilities transduce biochemical signals promote cell migration were severely impaired. The implicate interaction adhesion-dependent...
BAR domains are protein modules that bind to membranes and promote membrane curvature. One type of domain, the N-BAR contains an additional N-terminal amphipathic helix, which contributes membrane-binding bending activities. The only known N-BAR-domain proteins in budding yeast Saccharomyces cerevisiae, Rvs161 Rvs167, required for endocytosis. We have explored mechanism function endocytosis process using a combined biochemical genetic approach. show purified Rvs161-Rvs167 complex binds...
CCM3 mutations give rise to cerebral cavernous malformations (CCMs) of the vasculature through a mechanism that remains unclear. Interaction with germinal center kinase III (GCKIII) subfamily Sterile 20 protein kinases, MST4, STK24, and STK25, has been implicated in cardiovascular development zebrafish, raising possibility dysregulated GCKIII function may contribute etiology CCM disease. Here, we show amino-terminal region is necessary sufficient bind directly C-terminal tail proteins. This...
BRCC36 is a Zn2+-dependent deubiquitinating enzyme (DUB) that hydrolyzes lysine-63-linked ubiquitin chains as part of distinct macromolecular complexes participate in either interferon signaling or DNA-damage recognition. The MPN+ domain protein associates with pseudo DUB MPN– proteins KIAA0157 Abraxas, which are essential for enzymatic activity. To understand the basis regulation, we have solved structure an active BRCC36-KIAA0157 heterodimer and inactive homodimer. Structural functional...
The tumor suppressor and deubiquitinase (DUB) BAP1 its Drosophila ortholog Calypso assemble DUB complexes with the transcription regulators Additional sex combs-like (ASXL1, ASXL2, ASXL3) Asx respectively. ASXLs use their DEUBiquitinase ADaptor (DEUBAD) domain to stimulate BAP1/Calypso activity. Here we report that monoubiquitination of DEUBAD is a general feature Asx. promotes resulting in an increased stability which turn stimulates ASXL2 directly catalyzed by UBE2E family...