A5007319541- Cancer therapeutics and mechanisms
- Lung Cancer Research Studies
- Heat shock proteins research
- Glycosylation and Glycoproteins Research
- Chronic Myeloid Leukemia Treatments
- Endoplasmic Reticulum Stress and Disease
- Cancer-related Molecular Pathways
- ATP Synthase and ATPases Research
- Cell death mechanisms and regulation
- Biochemical and Molecular Research
- Toxin Mechanisms and Immunotoxins
- Protein Kinase Regulation and GTPase Signaling
- Bacillus and Francisella bacterial research
- Lung Cancer Treatments and Mutations
- Hemoglobin structure and function
- Neuroendocrine Tumor Research Advances
- Colorectal Cancer Treatments and Studies
- Bioactive Compounds and Antitumor Agents
- Monoclonal and Polyclonal Antibodies Research
- Protein Structure and Dynamics
- Neutropenia and Cancer Infections
- Fungal Plant Pathogen Control
- Quinazolinone synthesis and applications
- thermodynamics and calorimetric analyses
- Genomics, phytochemicals, and oxidative stress
Boston University
2011-2025
SRM Institute of Science and Technology
2024
Boston Medical Center
2005-2020
Nizam's Institute of Medical Sciences
2015
University of Chicago
2005-2013
University of Wisconsin–Madison
2013
OncoPlex Diagnostics (United States)
2013
University Medical Center
2005-2012
University of Mendoza
2007
Dana-Farber Cancer Institute
1994-2005
Cytochrome C is a mitochondrial protein that induces apoptosis when released into the cytosol or added to cell-free extracts. Here we show cells overexpress Bcl-2-related Bcl-x L fail accumulate cytosolic cytochrome undergo in response genotoxic stress. Coimmunoprecipitation studies demonstrate associates with C. binds directly and specifically not proapoptotic s protein. The results also blocks binding of . Our findings support role for protecting from by inhibiting availability cytosol.
The DF3/MUC1 mucin-like glycoprotein is aberrantly overexpressed in human breast carcinomas. functional role of DF3 unknown. present studies demonstrate that associates with β-catenin. Similar findings have been obtained for γ-catenin but not α-catenin. DF3, like E-cadherin and the adenomatous polyposis coli gene product, contains an SXXXXXSSL site responsible direct binding to results further interaction β-catenin dependent on cell adhesion. These signaling support a adhesion epithelial...
The DF3/MUC1 mucin-like glycoprotein is highly overexpressed in human carcinomas. Recent studies have demonstrated that the cytoplasmic domain of MUC1 interacts with β-catenin. Here we show associates glycogen synthase kinase 3β (GSK3β). GSK3β binds directly to an STDRSPYE site and phosphorylates serine adjacent proline. Phosphorylation by decreases binding β-catenin vitro vivo. GSK3β-mediated phosphorylation had no apparent effect on levels or transcriptional coactivation function results,...
Protein kinase Cdelta (PKCdelta) is proteolytically cleaved and activated at the onset of apoptosis induced by DNA-damaging agents, tumor necrosis factor, anti-Fas antibody. A role for PKCdelta in supported finding that overexpression catalytic fragment (PKCdelta CF) cells associated with appearance certain characteristics apoptosis. However, functional relationship between cleavage induction unknown. The present studies demonstrate associates constitutively DNA-dependent protein subunit...
Mucin 1 (MUC1) is a heterodimeric protein that aberrantly overexpressed on the surface of diverse human carcinomas and an attractive target for development mAb-based therapeutics. However, attempts at targeting shed MUC1 N-terminal subunit have been unsuccessful. We report here generation mAb 3D1 against nonshed oncogenic C-terminal (MUC1-C) subunit. show binds with low nM affinity to MUC1-C extracellular domain restricted α3 helix. reactivity selective MUC1-C-expressing cancer cell lines...
DNA topoisomerase I (topo I) is involved in the regulation of supercoiling, gene transcription, and rDNA recombination. However, little known about interactions between topo other nuclear proteins. We used affinity chromatography with a fusion protein to screen U-937 leukemic cell extracts have identified nucleolin as I-binding protein. Coimmunoprecipitation studies demonstrate that interaction direct. Furthermore, deletion analyses 166-210-amino acid region sufficient for nucleolin. Since...
Human U-937 myeloid leukemia cells were selected for resistance to increasing concentrations of the camptothecin derivative, 9-nitro-20(S)camptothecin (9-NC). The isolated single cell clone, designated U-937/CR, was approximately 20-fold resistant 9-NC. Analysis topoisomerase I (topo I) gene expression in U-937/CR demonstrated similar mRNA levels as compared with cells. Immunoblotting an anti-topo serum revealed reactive proteins at 100, 75, and 67 kDa which expressed same level parental...
Protein kinase C (PKC) δ is cleaved by caspase-3 to a kinase-active catalytic fragment (PKCδCF) in the apoptotic response of cells DNA damage. Expression PKCδCF contributes induction apoptosis mechanisms that are presently unknown. Here we demonstrate associates with p73β, structural and functional homologue p53 tumor suppressor. The results show phosphorylates p73β transactivation DNA-binding domains. One PKCδCF-phosphorylation site has been mapped Ser-289 domain. PKCδCF-mediated...
Titin, a giant protein spanning half the sarcomere, is responsible for passive and restoring forces in cardiac myofilaments during sarcomere elongation compression, respectively. In addition, titin has been implicated length-dependent activation that occurs stretched transition from diastole to systole. The purpose of this study was investigate role deactivation early diastole, when myocyte shortened below slack length. We developed novel vitro assay assess force (RF) by measuring velocity...
The ubiquitously expressed c-Abl tyrosine kinase is activated in the response of cells to genotoxic and oxidative stress. present study demonstrates that reactive oxygen species (ROS) induce targeting mitochondria. We show ROS-induced localization mitochondria dependent on activation protein C (PKC)δ function. Targeting associated with loss mitochondrial transmembrane potential. results also demonstrate necessary for depletion ATP a necrosis-like cell death. These findings indicate targets...
We have developed a molecular chaperone-based tumor vaccine that reverses the immune tolerance of cancer cells. Heat shock protein (HSP) 70 extracted from fusions dendritic (DC) and cells (HSP70.PC-F) possess superior properties such as stimulation DC maturation T cell proliferation over its counterpart More importantly, immunization mice with HSP70.PC-F resulted in cell-mediated response including significant increase CD8 induction effector memory was able to break unresponsiveness...
Many inducible transcription factors are regulated through batteries of posttranslational modifications that couple their activity to inducing stimuli. We have studied such regulation Heat Shock Factor 1 (HSF1), a key protein in control the heat shock response, and participant carcinogenisis, neurological health aging. As mechanisms involved intracellular HSF1 good its dysregulation disease still incomplete we investigating role regulation.In proteomic study binding partners, discovered...
Mucin 1 (MUC1) is a heterodimeric protein that aberrantly expressed in diverse human carcinomas and certain hematologic malignancies. The oncogenic MUC1 transmembrane C-terminal subunit (MUC1-C) functions part by transducing growth survival signals from cell surface receptors. However, little known about the structure of MUC1-C cytoplasmic domain as potential drug target. Using methods for structural predictions, our results indicate highly conserved CQCRRK sequence, which adjacent to...
217 Background: Chemotherapy plays an important role in the treatment of colorectal cancer. Irinotecan, a topoisomerase I inhibitor, is used therapies such as FOLFIRI and FOLFOXIRI. However, many patients become resistant to irinotecan, detailed mechanisms resistance are not fully understood. The aim develop new therapeutic strategies by elucidating irinotecan resistance. Methods: We vitro approach demonstrate mechanism topoI degradation. Immunohistochemistry staining was explore biomarker...
This study reports the synthesis of 5% Al-doped zinc oxide (ZnO) nanoparticles using sol-gel method, followed by a comprehensive analysis their structural and dielectric properties. X-ray diffraction (XRD) confirmed hexagonal wurtzite structure with lattice parameters = 3.277 Å c 5.257 Å, indicating successful Al³⁺ incorporation without impurity phases. Dielectric relaxation spectroscopy (DRS) revealed low real permittivity (ε' ≈ 0.97–1.0) an extremely loss (ε'' 10⁻¹³ to 10⁻¹²) over 400 kHz...
AbstractThe c-Abl protein tyrosine kinase is activated by certain DNA-damaging agents and regulates induction of the stress-activated c-Jun N-terminal (SAPK). Here we show that nuclear associates with MEK 1 (MEKK-1), an upstream effector SEK1→SAPK pathway, in response cells to genotoxic stress. The results demonstrate binds MEKK-1 phosphorylates vitro vivo. Transient-transfection studies wild-type kinase-inactive kinase-dependent activation MEKK-1. Moreover, activates DNA damage. also...