A5082175561- Advanced Proteomics Techniques and Applications
- Ubiquitin and proteasome pathways
- Mass Spectrometry Techniques and Applications
- Epigenetics and DNA Methylation
- Monoclonal and Polyclonal Antibodies Research
- Genomics and Chromatin Dynamics
- Cancer, Hypoxia, and Metabolism
- Cancer-related Molecular Pathways
- Histone Deacetylase Inhibitors Research
- Glycosylation and Glycoproteins Research
- interferon and immune responses
- Cancer-related gene regulation
- Protein Degradation and Inhibitors
- Cell death mechanisms and regulation
- Viral Infectious Diseases and Gene Expression in Insects
- Peptidase Inhibition and Analysis
- Metabolomics and Mass Spectrometry Studies
- Analytical Chemistry and Chromatography
- Axon Guidance and Neuronal Signaling
- Molecular Biology Techniques and Applications
- NF-κB Signaling Pathways
- T-cell and B-cell Immunology
- Phagocytosis and Immune Regulation
- Antimicrobial Resistance in Staphylococcus
- Immunotherapy and Immune Responses
Genentech
1999-2014
National Institutes of Health
1996-2010
National Cancer Institute
2000-2010
Center for Cancer Research
2010
University of California, Los Angeles
2007
Molecular Oncology (United States)
2004-2006
University of California, Davis
2004
California Institute of Technology
2004
Howard Hughes Medical Institute
2004
PDL BioPharma (United States)
2001
Caspase-8 is believed to play an obligatory role in apoptosis initiation by death receptors, but the of its structural relative, caspase-10, remains controversial. Although earlier evidence implicated caspase-10 signaling CD95L and Apo2L/TRAIL, recent studies indicated that these receptor ligands recruit caspase-8 not their death-inducing complex (DISC) even presence abundant caspase-10. We characterized a series caspase-10-specific antibodies found certain commercially available cross-react...
Production of type I interferon (IFN-I) is a critical host defense triggered by pattern-recognition receptors (PRRs) the innate immune system. Deubiquitinating enzyme A (DUBA), an ovarian tumor domain-containing deubiquitinating enzyme, was discovered in small interfering RNA–based screen as regulator IFN-I production. Reduction DUBA augmented PRR-induced response, whereas ectopic expression had converse effect. bound necrosis factor receptor–associated 3 (TRAF3), adaptor protein essential...
Arabidopsis thaliana De-etiolated-1 (AtDET1) is a highly conserved protein, with orthologs in vertebrate and invertebrate organisms. AtDET1 negatively regulates photomorphogenesis, but its biochemical mechanism function other species are unknown. We report that human DET1 (hDET1) promotes ubiquitination degradation of the proto-oncogenic transcription factor c-Jun by assembling multisubunit ubiquitin ligase containing DNA Damage Binding Protein-1 (DDB1), cullin 4A (CUL4A), Regulator...
Acetylation of histone H3 at lysine 27 is a well-defined marker enhancer activity. However, the functional impact this modification enhancers poorly understood. Here, we use chemical genetics approach to acutely block function cAMP response element binding protein (CREB) (CBP)/P300 bromodomain in models hematological malignancies and describe consequent loss H3K27Ac specifically from enhancers, despite continued presence CBP/P300 chromatin. Using dissect role identify critical for production...
A propensity for rewiring genetic and epigenetic regulatory networks, thus enabling sustained cell proliferation, suppression of apoptosis, the ability to evade immune system, is vital cancer propagation. An increased understanding how this achieved critical identifying or improving therapeutic interventions. In study, using acute myeloid leukemia (AML) human lines a custom CRISPR/Cas9 screening platform, we identify H3K9 methyltransferase SETDB1 as novel, negative regulator innate immunity....
Allele-specific motifs for the human MHC class I molecules, HLA-A1, A3, A11, and A24 were characterized by three complementary approaches. First, amino acid sequence analysis of eluted peptide pools from affinity purified molecules defined putative 9 or 10 acids in length bearing critical anchor residues at position 2 COOH-terminal. These distinct, with exception HLA-A3 A11 that very similar to each other. Second, correctness these was verified analyzing binding capacity polyalanine...
Protein ubiquitination provides an efficient and reversible mechanism to regulate cell cycle progression checkpoint control. Numerous regulatory proteins direct the addition of ubiquitin lysine residues on target proteins, these are countered by army deubiquitinating enzymes (DUBs). BRCA1-associated protein-1 (Bap1) is a carboxy-terminal hydrolase frequently mutated in lung sporadic breast tumors. Bap1 can suppress growth cancer cells athymic nude mice this requires its DUB activity. We show...
Ubiquitinated substrates can be recruited to macromolecular complexes through interactions between their covalently bound ubiquitin (Ub) signals and Ub receptor proteins. To develop a functional understanding of the system in vivo, methods are needed determine composition on individual protein mixtures. Mass spectrometry has emerged as an important tool for characterizing various forms Ub. In Ubiquitin-AQUA approach, synthetic isotopically labeled internal standard peptides used quantify...
Chromatin immunoprecipitation and DNA sequencing (ChIP-seq) has been instrumental in inferring the roles of histone post-translational modifications regulation transcription, chromatin compaction other cellular processes that require modulation structure. However, analysis ChIP-seq data is challenging when manipulation a chromatin-modifying enzyme significantly affects global levels modifications. For example, small molecule inhibition methyltransferase EZH2 reduces H3 lysine 27...
NLRC4 and NLRP3, of the NOD-like receptor (NLR) family intracellular proteins, are expressed in innate immune cells thought to nucleate distinct inflammasome complexes that promote caspase-1 activation, secretion proinflammatory cytokines IL-1β IL-18, a form cell death termed pyroptosis. We show NLRP3 associates with macrophages infected Salmonella typhimurium or transfected flagellin. The significance interaction between NACHT domain was revealed when Nlrc4(S533A/S533A) bone marrow-derived...
Accumulating preclinical and clinical evidence implicates epithelial-mesenchymal transition (EMT) in acquired resistance to anticancer drugs; however, mechanisms by which the mesenchymal state determines drug remain unknown. To explore a potential role for altered cellular metabolism EMT associated resistance, we analyzed metabolome transcriptome of three lung cancer cell lines that were rendered resistant following experimental induction EMT. This analysis revealed metabolic rewiring during...
Alzheimer's disease (AD) is the leading cause of dementia affecting greater than 26 million people worldwide. Although cerebrospinal fluid (CSF) levels Aβ42, tau, and p-tau181 are well established as diagnostic biomarkers AD, there a need for additional CSF neuronal function that continue to change during progression could be used pharmacodynamic measures in clinical trials. Multiple proteomic discovery experiments have reported range differ between AD control subjects. These potential...
Hepatitis C virus (HCV) infection is a major cause of liver disease and hepatocellular carcinoma. Glycan shielding has been proposed to be mechanism by which HCV masks broadly neutralizing epitopes on its viral glycoproteins. However, the role altered glycosylation in resistance antibodies not fully understood. Here, we have generated potent hu5B3.v3 MRCT10.v362 that, similar previously described AP33 HCV1, bind highly conserved linear epitope E2. We utilize combination vitro selections...
Engineered destruction of target proteins by recruitment to the cell's degradation machinery has emerged as a promising strategy in drug discovery. The majority molecules that facilitate targeted do so via select number ubiquitin ligases, restricting this therapeutic approach tissue types express requisite ligase. Here, we describe new protein through direct substrate 26S proteasome. proteolytic complex is essential and abundantly expressed all cells; however, proteasomal ligands remain...