A5024483127- Heat shock proteins research
- thermodynamics and calorimetric analyses
- Endoplasmic Reticulum Stress and Disease
- Viral Infectious Diseases and Gene Expression in Insects
- Protein Structure and Dynamics
- Genetics, Aging, and Longevity in Model Organisms
- Physiological and biochemical adaptations
- Cancer, Hypoxia, and Metabolism
- HER2/EGFR in Cancer Research
- Virus-based gene therapy research
- Metabolism, Diabetes, and Cancer
- Herpesvirus Infections and Treatments
- Toxin Mechanisms and Immunotoxins
- Neurobiology and Insect Physiology Research
- Viral gastroenteritis research and epidemiology
- Amino Acid Enzymes and Metabolism
- Influenza Virus Research Studies
- Enzyme Structure and Function
- Insect and Pesticide Research
- Drug-Induced Hepatotoxicity and Protection
- Insect Resistance and Genetics
- Polyamine Metabolism and Applications
- CRISPR and Genetic Engineering
- Immunotherapy and Immune Responses
- Computational Drug Discovery Methods
University of Florida
2013-2018
Florida College
2015-2018
University of Colorado Denver
2011
Emory University
2011
University of South Alabama
2011
University of Oslo
2011
The University of Texas MD Anderson Cancer Center
2011
University of Miami
1994-2005
University of Florida Health Science Center
1997
University of California, San Francisco
1995
Heat shock protein (hsp) genes, a group of ubiquitous are activated by various metabolic stresses. The suggestion that denaturation intracellular proteins may be produced the stresses and then signal activation hsp genes was examined co-injection purified into frog oocytes. Activation observed if were denatured prior to injection but not they introduced in their native form. Furthermore, abnormal heat appears occur common mechanism. A model for transcriptional regulation is based on...
The promoters of heat shock protein genes are among the best-studied inducible eucaryotic promoters. Regions responsible for regulation have been identified previously by deletion experiments with several different genes. In this paper critical importance two novel features regulatory elements was investigated. First, were modular and, as a consequence, displayed characteristic 5-nucleotide periodicity produced multiple GAA blocks that arranged in alternating orientations and at 2-nucleotide...
Transcriptional activity of heat shock (hsp) genes is controlled by a heat-activated, group-specific transcription factor(s) recognizing arrays inverted repeats the element NGAAN. To date for two human factors, HSF1 and HSF2, have been isolated. define their properties as well changes they undergo during stress activation, we prepared polyclonal antibodies to these factors. Using tools, shown that HeLa cells constitutively synthesize HSF1, but were unable detect HSF2. In unstressed present...
Trastuzumab shows remarkable efficacy in treatment of ErbB2-positive breast cancers when used alone or combination with other chemotherapeutics. However, acquired resistance develops most treated patients, necessitating alternate strategies. Increased aerobic glycolysis is a hallmark cancer and inhibition may offer promising strategy to preferentially kill cells. In this study, we investigated the antitumor effects trastuzumab inhibitors cancer. We found that inhibits via downregulation heat...
Heat shock genes encode proteins (hsp's) that play important structural roles under normal circumstances and are essential to the cells' ability survive environmental insults. Evidence is presented herein transcriptional regulation of hsp gene expression linked with overall protein synthesis as well accumulation denatured by stressful events. The factor connects three processes appears be one hsp's, presumably a member(s) hsp70 family. Biochemical experiments demonstrate complexes containing...
Heat shock factor (HSF/HSF1) not only is the transcription primarily responsible for transcriptional response of cells to physical and chemical stress but also coregulates other important signaling pathways. The mediates stress-induced expression heat or proteins (HSPs). HSF/HSF1 inactive in unstressed activated during stress. Activation accompanied by hyperphosphorylation factor. regulatory importance this phosphorylation has remained incompletely understood. Several previous studies on...
Upon heat stress, monomeric human shock transcription factor 1 (hHSF1) is converted to a trimer, acquires DNA-binding ability, transported the nucleus, and becomes transcriptionally competent. It was not known previously whether these regulatory changes are caused by single activation event or they occur independently from one another, providing multilayered control that may prevent inadvertant of hHSF1. Comparison wild-type mutant hHSF1 expressed in Xenopus oocytes HeLa cells suggested...
In the absence of stress, human heat shock factor 1 (hHSF1) is in its unactivated form. hHSF1 polypeptide a dynamic heterocomplex with Hsp90 and incapable specifically binding DNA. When cells are stressed, assembly disrupted. Unbound homotrimerizes, acquires DNA activity, concentrates nucleus, but remains transcriptionally inactive. A subsequent reaction converts this inactive, trimeric form into active, hyperphosphorylated transcription factor. Subsequent to stressful event, deactivated...
Heat stress regulation of human heat shock genes is mediated by transcription factor hHSF1, which contains three 4-3 hydrophobic repeats (LZ1 to LZ3). In unstressed cells (37 degrees C), hHSF1 appears be in an inactive, monomeric state that may maintained through intramolecular interactions stabilized transient interaction with hsp70. (39 42 C) disrupts these interactions, and homotrimerizes acquires element DNA-binding ability. expressed Xenopus oocytes also assumes a monomeric,...
The promoters of heat shock protein genes are among the best-studied inducible eucaryotic promoters. Regions responsible for regulation have been identified previously by deletion experiments with several different genes. In this paper critical importance two novel features regulatory elements was investigated. First, were modular and, as a consequence, displayed characteristic 5-nucleotide periodicity produced multiple GAA blocks that arranged in alternating orientations and at 2-nucleotide...
An oocyte expression system was used to test the relation between a complementary DNA (cDNA) clone encoding liver gap junction protein and cell-cell channels. Total polyadenylated messenger RNA injected into oocytes induced channels paired oocytes. This induction blocked by simultaneous injection of antisense transcribed from cDNA. Messenger selected hybridization cDNA translated in pairs yielded higher junctional conductance than unselected RNA. Cell-cell were also formed when cloned...
A human 70-kDa heat shock protein (hsp70) gene segment has been isolated. The contains 3.15 kilobase pairs (kbp) of 5' nontranscribed sequence, an RNA leader 119 bp, and a protein-coding region 741 bp. sequence shows high degree homology to hsp70 sequences from other species. Expression experiments in Xenopus oocytes mammalian cells indicate that includes only 105 bp all elements required for the efficient heat-controlled expression gene. Two adjacent identical elements, which are partly...
We previously showed that the ability of human B lymphocytes to elicit a cytoprotective heat shock response when confronted by or other stresses was dependent upon state cell activation. This unexpected, considering highly conserved nature and widely held belief all nonmutated mature cells were capable eliciting stressed. To elucidate mechanism which activation primes respond stresses, we examined transcription factor 1 (hHSF1) in since this appears be solely responsible for stress-induced...
In the course of its activation by heat and other stresses, inactive monomer human shock transcription factor 1 (HSF1) is converted to a DNA-binding homotrimer hyperphosphorylated. At least four Ser/Thr residues in HSF1 appeared be inducibly phosphorylated during shock. protein kinase inhibitors inhibited, phosphatase inhibitor calyculin A phorbol ester enhanced, hsp70-CAT reporter gene expression but not element DNA binding activity HeLa cells undergoing moderate Calyculin (5-20 nM) caused...
We have previously shown that the human 70-kilodalton heat shock protein gene (hsp70) is induced by adenovirus E1A product and during S-G2 phase of cell cycle. In this study, we investigated effect on expression other hsp genes. A encoding one form hsp89 (hsp89 alpha) was activated an infection with kinetics similar to those activation hsp70. The induction required a functional gene. However, transcript not cycle regulated. Genes another hsp27 were or Further examination hsp70 revealed...
Xenopus cells, like many other eukaryotic respond to heat treatments by increasing the rate of synthesis a few characteristic proteins, shock proteins. Because generality this response, it seemed possible examine expression isolated genes in heterologous system. Phage 122 DNA, containing two identical coding for Drosophila 70,000-dalton protein (hsp70 genes), was microinjected into oocyte nuclei. The hsp70 are transcribed efficiently heat-treated oocytes (35-37 degrees C) give RNA correct...
Comparative modeling of the DNA-binding domain human HSF1 facilitated prediction possible binding pockets for small molecules and definition corresponding pharmacophores. In silico screening a large library lead-like compounds identified set that satisfied pharmacophoric criteria, selection which was purchased to populate biased sublibrary. A discriminating cell-based assay compound 001, subjected systematic analysis structure-activity relationships, resulting in development 115 (IHSF115)....
Transcriptional activity of heat shock (hsp) genes is controlled by a heat-activated, group-specific transcription factor(s) recognizing arrays inverted repeats the element NGAAN. To date for two human factors, HSF1 and HSF2, have been isolated. define their properties as well changes they undergo during stress activation, we prepared polyclonal antibodies to these factors. Using tools, shown that HeLa cells constitutively synthesize HSF1, but were unable detect HSF2. In unstressed present...