0000000000938963
AUTHOR
Giosalba Burgio
showing 51 related works from this author
The nucleosome-remodeling ATPase ISWI is regulated by poly-ADP-ribosylation.
2008
ATP-dependent nucleosome-remodeling enzymes and covalent modifiers of chromatin set the functional state of chromatin. However, how these enzymatic activities are coordinated in the nucleus is largely unknown. We found that the evolutionary conserved nucleosome-remodeling ATPase ISWI and the poly-ADP-ribose polymerase PARP genetically interact. We present evidence showing that ISWI is target of poly-ADP-ribosylation. Poly-ADP-ribosylation counteracts ISWI function in vitro and in vivo. Our work suggests that ISWI is a physiological target of PARP and that poly-ADP-ribosylation can be a new, important post-translational modification regulating the activity of ATP-dependent nucleosome remodel…
P/CAF-mediated spermidine acetylation regulates histone acetyltransferase activity
2016
Histones and polyamines are important determinants of the chromatin structure. Histones form the core of nucleosome particles and their modification by acetylation of N-terminal tails is involved in chromatin structural changes and transcriptional regulation. Polyamines, including spermidine, are also targets of both cytoplasmic and nuclear acetylation, which in turn alters their affinity for DNA and nucleosomes. Previous studies report the interplay between polyamines metabolism and levels of histone acetylation, but the molecular basis of this effect is still unclear. In this work, we have analyzed the in vitro effect of spermidine on histone H3 acetylation catalyzed by P/CAF, a highly co…
Hsp60 is actively secreted by human tumor cells
2010
Background Hsp60, a Group I mitochondrial chaperonin, is classically considered an intracellular chaperone with residence in the mitochondria; nonetheless, in the last few years it has been found extracellularly as well as in the cell membrane. Important questions remain pertaining to extracellular Hsp60 such as how generalized is its occurrence outside cells, what are its extracellular functions and the translocation mechanisms that transport the chaperone outside of the cell. These questions are particularly relevant for cancer biology since it is believed that extracellular chaperones, like Hsp70, may play an active role in tumor growth and dissemination. Methodology/Principal Findings S…
The Odyssey of Hsp60 from Tumor Cells to Other Destinations Includes Plasma Membrane-Associated Stages and Golgi and Exosomal Protein-Trafficking Mod…
2012
BACKGROUND: In a previous work we showed for the first time that human tumor cells secrete Hsp60 via exosomes, which are considered immunologically active microvesicles involved in tumor progression. This finding raised questions concerning the route followed by Hsp60 to reach the exosomes, its location in them, and whether Hsp60 can be secreted also via other mechanisms, e.g., by the Golgi. We addressed these issues in the work presented here. PRINCIPAL FINDINGS: We found that Hsp60 localizes in the tumor cell plasma membrane, is associated with lipid rafts, and ends up in the exosomal membrane. We also found evidence that Hsp60 localizes in the Golgi apparatus and its secretion is prevent…
Hsp60 secretion and migration from cancer cells: a proposal for a multistage pathway
2012
Chromatin remodeling regulation by small molecules and metabolites.
2010
The eukaryotic genome is a highly organized nucleoprotein structure comprising of DNA, histones, non-histone proteins, and RNAs, referred to as chromatin. The chromatin exists as a dynamic entity, shuttling between the open and closed forms at specific nuclear regions and loci based on the requirement of the cell. This dynamicity is essential for the various DNA-templated phenomena like transcription, replication, and repair and is achieved through the activity of ATP-dependent chromatin remodeling complexes and covalent modifiers of chromatin. A growing body of data indicates that chromatin enzymatic activities are finely and specifically regulated by a variety of small molecules derived f…
Human Hsp60 with Its Mitochondrial Import Signal Occurs in Solution as Heptamers and Tetradecamers Remarkably Stable over a Wide Range of Concentrati…
2014
It has been established that Hsp60 can accumulate in the cytosol in various pathological conditions, including cancer and chronic inflammatory diseases. Part or all of the cytosolic Hsp60 could be naive, namely, bear the mitochondrial import signal (MIS), but neither the structure nor the in solution oligomeric organization of this cytosolic molecule has still been elucidated. Here we present a detailed study of the structure and self-organization of naive cytosolic Hsp60 in solution. Results were obtained by different biophysical methods (light and X ray scattering, single molecule spectroscopy and hydrodynamics) that all together allowed us to assay a wide range of concentrations of Hsp60…
Functional antagonism between histone H3K4 demethylases in vivo
2011
Dynamic regulation of histone modifications is critical during development, and aberrant activity of chromatin-modifying enzymes has been associated with diseases such as cancer. Histone demethylases have been shown to play a key role in eukaryotic gene transcription; however, little is known about how their activities are coordinated in vivo to regulate specific biological processes. In Drosophila, two enzymes, dLsd1 (Drosophila ortholog of lysine-specific demethylase 1) and Lid (little imaginal discs), demethylate histone H3 at Lys 4 (H3K4), a residue whose methylation is associated with actively transcribed genes. Our studies show that compound mutation of Lid and dLsd1 results in increa…
The nucleosome remodeling factor ISWI functionally interacts with an evolutionarily conserved network of cellular factors
2010
Abstract ISWI is an evolutionarily conserved ATP-dependent chromatin remodeling factor playing central roles in DNA replication, RNA transcription, and chromosome organization. The variety of biological functions dependent on ISWI suggests that its activity could be highly regulated. Our group has previously isolated and characterized new cellular activities that positively regulate ISWI in Drosophila melanogaster. To identify factors that antagonize ISWI activity we developed a novel in vivo eye-based assay to screen for genetic suppressors of ISWI. Our screen revealed that ISWI interacts with an evolutionarily conserved network of cellular and nuclear factors that escaped previous genetic…
Genetic identification of a network of factors that functionally interact with the nucleosome remodeling ATPase ISWI.
2008
Nucleosome remodeling and covalent modifications of histones play fundamental roles in chromatin structure and function. However, much remains to be learned about how the action of ATP-dependent chromatin remodeling factors and histone-modifying enzymes is coordinated to modulate chromatin organization and transcription. The evolutionarily conserved ATP-dependent chromatin-remodeling factor ISWI plays essential roles in chromosome organization, DNA replication, and transcription regulation. To gain insight into regulation and mechanism of action of ISWI, we conducted an unbiased genetic screen to identify factors with which it interacts in vivo. We found that ISWI interacts with a network o…
The histone deacetylase Rpd3 regulates the heterochromatin structure of Drosophila telomeres
2011
Telomeres are specialized structures at the end of eukaryotic chromosomes that are required to preserve genome integrity, chromosome stability and nuclear architecture. Telomere maintenance and function are established epigenetically in several eukaryotes. However, the exact chromatin enzymatic modifications regulating telomere homeostasis are poorly understood. In Drosophila melanogaster, telomere length and stability are maintained through the retrotransposition of specialized telomeric sequences and by the specific loading of protecting capping proteins, respectively. Here, we show that the loss of the essential and evolutionarily conserved histone deacetylase Rpd3, the homolog of mammal…
Structure and Stability of Hsp60 and Groel in Solution
2016
Molecular chaperones are a class of proteins able to prevent non-specific aggregation of mitochondrial proteins and to promote their proper folding. Among them, human Hsp60 is currently considered as a ubiquitous molecule with multiple roles both in maintaining health conditions and as a trigger of several diseases. Of particular interest is its role in neurodegenerative disorders since it is able to inhibit the formation of amyloid fibrils.Hsp60 structure was considered, until recent years, analogue to the one of its bacterial homolog GroEL, one of the most investigated chaperones, whose crystallographic structure is a homo-tetradecamer, made up of two seven member rings. On the contrary, …
A conserved role for the mitochondrial citrate transporter Sea/SLC25A1 in the maintenance of chromosome integrity.
2009
Histone acetylation plays essential roles in cell cycle progression, DNA repair, gene expression and silencing. Although the knowledge regarding the roles of acetylation of histone lysine residues is rapidly growing, very little is known about the biochemical pathways providing the nucleus with metabolites necessary for physiological chromatin acetylation. Here, we show that mutations in the scheggia (sea)-encoded Sea protein, the Drosophila ortholog of the human mitochondrial citrate carrier Solute carrier 25 A1 (SLC25A1), impair citrate transport from mitochondria to the cytosol. Interestingly, inhibition of sea expression results in extensive chromosome breakage in mitotic cells and indu…
Functional Interaction between ISWI and Covalent Modifiers of Chromatin
2006
Extracellular release of HSP60 from tumor cells occurs via various secretory pathways
2008
Immuno-Fluorescence (IF) on interphase polytene chromosomes of Drosophila melanogaster
2008
A Drosophila model to study the human multysistemic disease Williams Beuren sindrome
2005
“Acetilazione di p53 e degli istoni nell’apoptosi indotta dal SAHA in cellule di epatoma umano HepG2”
2006
EXTRACELLULAR RELEASE OF HSP60 FROM TUMOR CELLS
2008
Functional Regulation of the Nucleosome Remodeling ATPase ISWI by PARP
2007
The Nucleosome Remodeling ATPase ISWI is Regulated by poly-ADP-ribosylation
2008
Functional Interaction between Remodelers and Covalent Modifiers of Chromatin
2006
Exosome Involvment in Hsp60 secretion by tumor cells.
2011
Loss of the Sin3A/Rpd3 Histone De-Acetylase Complex Causes Polytene Chromosome Telomeric Fusions
2009
Regulation of PCAF Activity by Spermidine
2011
Histones and polyamines are important determinants of chromatin structure. Histones are the core of nucleosome particles and their modification by acetylation of N-terminal tails is involved in chromatin structural changes and transcriptional modulation. Polyamines also, including spermidine, are targets of both nuclear and cytoplasmic acetylation, which in turn alters their affinity for DNA and nucleosomes. Previous studies report an interplay existing between polyamines metabolism and levels, and histone acetylation. The relationship between polyamines and histone epigenetics in vivo has been considered in various models of ageing through epigenetic modifications, induction of autophagy a…
Functional Interaction between the Nucleosome Remodeling Factor ISWI and Covalent Modifiers of Chromatin
2007
Loss of the Sin3A/Rpd3 Histone De-Acetylase Complex Causes Telomeric Fusions
2009
Trafficking and secretion patterns of Hsp60 in tumor cells.
2012
Un Modello in Drosophila per Studiare la Sindrome di Williams-Beuren
2005
The histone deacetylase Rpd3 regulates telomeric heterochromatin structure of polytene chromosomes
2010
UbcD1 knock-down increases chromosomes condensation defects caused by loss of ISWI function
2010
La Perdita di Funzione del Complesso di Deacetilazione Istonica Sin3A/Rpd3 Causa Fusioni Telomeriche
2008
PCAF catalyzes tha acetylation of spermidine to N8-acetylspermidine and regulates its acetylating activity on histones
2011
Post-transcriptional histone acetylation is a well known process playing a crucial role in chromatin assembly and transcription. Here, we report that PCAF, a highly conserved histone acetyltransferase (HAT), can efficiently catalyze acetylation of spermidine to N8-acetylspermidine, at low concentration. Remarkably, we found that spermidine at higher concentration can also inhibit PCAF HAT activity directed against histone H3 in vitro, confirming the in vivo data referred by Eisenberg et al. on the spermidine induced inhibition of H3 acetylation. Surprisingly when we performed HAT assay experiments at low spermidine concentration we observed an activating effect on PCAF on H3 acetylation. Ou…
Hsp60 from cancer cells can reach near and distant targets: A proposal for a multistage pathway
2011
Cancer cells have means to influence other cells in their vicinity and distant, and in this signal-delivering mechanisms the chaperonin Hsp60 plays a role, which is currently being recognized as potentially crucial for the growth and dissemination of at least certain types of tumors. In order to arrive at its destination, Hsp60, a typical resident of mitochondria in normal and tumor cells, leaves the organelle and reaches the blood. In the latter, Hsp60 can travel and arrive at targets situated far away from its origin. The details of the route followed by Hsp60 and their molecular mechanisms have not yet been fully elucidated. We investigated Hsp60 levels and secretion in normal and tumor …
A Drosophila Model to Study the Human Multisystemic Disease Williams-Beuren Syndrome
2005
A Genetic Screen for Dominant Modifiers of ISWI Reveals Functional Interactions with the SIN3A/RPD3 Complex
2007
Loss of ISWI in Drosophila immaginal discs causes cell cycle defects
2006
UbcD1 is a Histone H2B Ubiquitin-Conjugating Enzyme Essential for Global Chromatin Structure and Gene Expression Regulation
2014
UbcD1: from telomere capping to global chromatin regulation
2012
Circulating exosomal Hsp60 as a new marker of colon cancer.
2012
SIN3A genetically and physically interacts with ISWI
2005
Chromatin remodeling disease: a functional link with poly-ADP-Ribosylation
2009
ISWI Functionally Interacts with the SIN3A/RPD3 Complex
2007
Chromatin remodeling redulation by small molecules and metabolites
2010
UbcD1: from telomere capping to global heterochromatin regulation
2012
A new epigenetic cross-talk links effete and iswi in determining chromatin structure
2011
Naïve Hsp60, similarly to GroEL, oligomerizes to build heptameric and tetradecameric structures.
2013
The acetylation of spermidine catalyzed by P/CAF regulates its acetyltransferase activity versus histones
2010
Transcriptional regulation in eukaryotes occurs within a chromatin setting and is strongly inhibited by nucleosomal barriers imposed by histone proteins. Among the well-known covalent modifications of chromatin, the reversible acetylation of specific lysine residues of histones, catalyzed by several acetyltransferase and deacetylases, has been linked to many biological processes including transcriptional regulation. Indeed, many transcriptional coactivators possess histone acetyltransferase (HAT) activity (1). Functional interactions between HAT and polyamines have been previously reported. In particular, it has been shown that polyamines facilitate oligomerization of nucleosomal arrays in …