A5089421025- NF-κB Signaling Pathways
- S100 Proteins and Annexins
- Immune Response and Inflammation
- Cytokine Signaling Pathways and Interactions
- Advanced Proteomics Techniques and Applications
- interferon and immune responses
- Mass Spectrometry Techniques and Applications
- Cell death mechanisms and regulation
- Autophagy in Disease and Therapy
- Epigenetics and DNA Methylation
- Endoplasmic Reticulum Stress and Disease
- Cancer Cells and Metastasis
- Protein Kinase Regulation and GTPase Signaling
- Prostate Cancer Treatment and Research
- Neonatal Respiratory Health Research
- Viral Infectious Diseases and Gene Expression in Insects
- Estrogen and related hormone effects
- Heat shock proteins research
- Analytical Chemistry and Chromatography
- Inhalation and Respiratory Drug Delivery
- Sulfur Compounds in Biology
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Drug-Induced Hepatotoxicity and Protection
- Trace Elements in Health
- DNA Repair Mechanisms
University of Southern California
2012-2025
USC Norris Comprehensive Cancer Center
2001-2025
Medical College of Wisconsin
2014
Bipar
2014
Children's Hospital of Los Angeles
2008
University of California, San Diego
1994-2005
The University of Texas Southwestern Medical Center
2005
Keck Hospital of USC
2004
California Institute of Technology
1994-1997
University of Zurich
1993
Reliable identification of posttranslational modifications is key to understanding various cellular regulatory processes. We describe a tool, InsPecT, identify using tandem mass spectrometry data. InsPecT constructs database filters that proved be very successful in genomics searches. Given an MS/MS spectrum S and D, filter selects small fraction D guaranteed (with high probability) contain peptide produced S. uses sequence tags as efficient reduce the size by few orders magnitude while...
Transcription factor AP-1 transduces environmental signals to the transcriptional machinery. To ensure a quick response yet maintain tight control over target genes, activity is likely be negatively regulated in nonstimulated cells. identify proteins that interact with Jun subunits of and repress its activity, we developed novel screen for detecting protein-protein interactions not based on readout. In this system, mammalian guanyl nucleotide exchange (GEF) Sos recruited Saccharomyces...
A large protein complex mediates the phosphorylation of inhibitor κB (IκB), which results in activation nuclear factor (NF-κB). Two subunits this complex, IκB kinase α (IKKα) and β (IKKβ), are required for NF-κB activation. Purified recombinant IKKα IKKβ expressed insect cells were used to demonstrate that each can directly phosphorylate proteins. found form both homodimers heterodimers. Both phosphorylated bound more efficiently than they free IκB. This result explains how accumulate IKK is...
Reactive oxygen species (ROS) are important second messengers generated in response to many types of environmental stress. In this setting, changes intracellular ROS can activate signal transduction pathways that influence how cells react their environment. sepsis, a dynamic proinflammatory cellular bacterial toxins (<i>e.g.</i> lipopolysaccharide or LPS) leads widespread organ damage and death. The present study demonstrates for the first time activation Rac1 (a GTP-binding protein),...
Gaseous signaling molecules such as hydrogen sulfide (H2S) are produced endogenously and mediate effects through diverse mechanisms. H2S is one gasotransmitters that regulates multiple pathways in mammalian cells, abnormal metabolism has been linked to defects bone homeostasis. Here, we demonstrate marrow mesenchymal stem cells (BMMSCs) produce order regulate their self-renewal osteogenic differentiation, deficiency results BMMSC differentiation. causes aberrant intracellular Ca(2+) influx...
Protein disulfide isomerase (PDI), an endoplasmic reticulum chaperone protein, catalyzes bond breakage, formation, and rearrangement. The effect of PDI inhibition on ovarian cancer progression is not yet clear, there a need for potent, selective, safe small-molecule inhibitors PDI. Here, we report class propynoic acid carbamoyl methyl amides (PACMAs) that are active against panel human cell lines. Using fluorescent derivatives, 2D gel electrophoresis, MS, established PACMA 31, one the most...
Significance Endoplasmic reticulum (ER) stress-mediated relocalization of ER chaperones to the cell surface allows cells expand their functionality beyond ER, impacting survival, death, migration, and immunity. However, little is known about underlying mechanisms interacting partners on surface. Both protooncogene tyrosine-protein kinase SRC TGF-β are important players in signaling, growth, apoptosis, survival. Our discoveries that activation driving force escape luminal proteins via...
Iron chelators inhibit endotoxin-induced NF-κB activation in hepatic macrophages (HMs), suggesting a role for the intracellular chelatable pool of iron activation. The present study tested this hypothesis. Analysis Fe59-loaded HMs stimulated with lipopolysaccharide (LPS), revealed previously unreported, transient rise low molecular weight (LMW)·Fe59complex ([LMW·Fe]i) at ≤2 min returning to basal level within 15 min. [LMW·Fe]i response preceded IκB kinase (IKK) (≥15 min) and (≥30...
The <i>tax</i> gene product of human T-cell leukemia virus I induces aberrant expression various cellular genes, which contributes to transformation host cells. Induction many Tax target genes is mediated through transcription factor NF-κB. Here we show that triggers activation protein kinases, IκB kinase α (IKKα) and IKKβ, phosphorylate the NF-κB inhibitory IκBα, resulting in its degradation activation. Constitutive IKK occurs both Tax-transfected I-infected T We further demonstrate...
Vascular endothelial cells (ECs), forming a boundary between the circulating blood and vessel wall, are constantly subjected to fluid shear stress due flow. The aim of this study was determine role recently identified IκB kinases (IKKs) in activation NF-κB elucidate upstream signaling mechanism that mediates IKK activation. Our results demonstrate IKKs ECs activated by rapid transient manner. This is followed degradation translocation into nucleus. Transfection plasmids encoding catalytic...
During V(D)J recombination, the RAG proteins create DNA hairpins at V, D, or J coding ends, and structure-specific nuclease Artemis is essential to open these prior joining. also an endonuclease for 5' 3' overhangs many double strand breaks caused by ionizing radiation, functions as part of nonhomologous end joining pathway in repairing these. All activities require activation protein interaction with phosphorylation DNA-dependent kinase catalytic subunit (DNA-PKcs). In this study, we have...
10.1152/ajpgi.00108. 2002.— Iron exacerbates various types of liver injury in which nuclear factor (NF)-κB-driven genes are implicated. This study tested a hypothesis that iron directly elicits the signaling required for activation NF-κB and stimulation tumor necrosis (TNF)-α gene expression Kupffer cells. Addition Fe 2+ but not 3+ (∼5–50 μM) to cultured rat cells increased TNF-α release promoter activity NF-κB-dependent manner. Cu + stimulated protein with less potency. caused disappearance...
Annexin A1 (AnxA1), a phospholipid-binding protein and regulator of glucocorticoid-induced inflammatory signaling, has implications in cancer. Here, role for AnxA1 prostate adenocarcinoma was determined using primary cultures tumor cell line (cE1), all derived from the conditional Pten deletion mouse model secretion by prostate-derived cancer-associated fibroblasts (CAF) significantly higher than normal (NPF). Prostate cells were sorted to enrich epithelial subpopulations based on...
Aims: We showed that chronic cholestatic liver injury induced the expression of c-Myc but suppressed glutamate-cysteine ligase (GCL, composed catalytic and modifier subunits GCLC GCLM, respectively). This was associated with reduced nuclear antioxidant response element (ARE) binding by factor-erythroid 2 related factor (Nrf2). Here, we examined whether is involved in this process. Results: Similar to bile duct ligation (BDL), lithocholic acid (LCA) treatment vivo GCL at day 14. Nrf2 ARE fell...
We have previously demonstrated that neuroblastoma cells increase the expression of interleukin-6 by bone marrow stromal and stimulation does not require cell-cell contact. In this study we report purification identification a protein secreted stimulates production cells. Using series chromatographic steps including heparin-affinity, ion exchange, molecular sieve chromatography followed trypsin digestion liquid tandem mass spectrometry, identified in serum-free conditioned medium several...