Marcella Bonanomi

Marcella Bonanomi
Università degli Studi di Milano-Bicocca | UNIMIB · Department of Biotechnology and Biosciences

PhD

About

33
Publications
3,300
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328
Citations
Additional affiliations
January 2011 - December 2013
Università degli Studi di Milano-Bicocca
Position
  • PhD Student

Publications

Publications (33)
Article
Full-text available
Cyclin-dependent kinase 12 (CDK12) overexpression is implicated in breast cancer, but whether it has a primary or only a cooperative tumorigenic role is unclear. Here, we show that transgenic CDK12 overexpression in the mouse mammary gland per se is sufficient to drive the emergence of multiple and multifocal tumors, while, in cooperation with know...
Article
Polystyrene is a thermoplastic polymer widely used in commercial products. Like all plastics, polystyrene can be degraded into microplastic and nanoplastic particles and ingested via food chain contamination. Although the ecological impact due to plastic contamination is well known, there are no studies indicating a carcinogenic potential of polyst...
Article
Full-text available
Metabolism is directly and indirectly fine-tuned by a complex web of interacting regulatory mechanisms that fall into two major classes. On the one hand, the expression level of the catalyzing enzyme sets the maximal theoretical flux level (i.e., the net rate of the reaction) for each enzyme-controlled reaction. On the other hand, metabolic regulat...
Article
Full-text available
Rewiring glucose metabolism toward aerobic glycolysis provides cancer cells with a rapid generation of pyruvate, ATP, and NADH, while pyruvate oxidation to lactate guarantees refueling of oxidized NAD+ to sustain glycolysis. CtPB2, an NADH-dependent transcriptional co-regulator, has been proposed to work as an NADH sensor, linking metabolism to epi...
Preprint
Full-text available
Metabolism is directly and indirectly fine-tuned by a complex web of interacting regulatory mechanisms that fall into two major classes. First, metabolic regulation controls metabolic fluxes (i.e., the rate of individual metabolic reactions) through the interactions of metabolites (substrates, cofactors, allosteric modulators) with the responsible...
Article
Zebrafish encodes several sialidases belonging to the NEU3 group, the plasma membrane-associated member of the family with high specificity toward ganglioside substrates. Neu3.1, Neu3.2 and Neu 3.3 have been expressed in E. coli and purified using the pGEX-2T expression system. Although all the enzymes are expressed by bacterial cells, Neu3.1 forme...
Article
Full-text available
The relevant role of pentose phosphate pathway (PPP) in cancer metabolic reprogramming has been usually outlined by studying glucose-6-phosphate dehydrogenase (G6PD). However, recent evidence suggests an unexpected role for a less characterized PPP, triggered by hexose-6-phosphate dehydrogenase (H6PD) within the endoplasmic reticulum (ER). Studying...
Article
Full-text available
Liver cancer is one of the most common cancer worldwide with a high mortality. Methionine is an essential amino acid required for normal development and cell growth, is mainly metabolized in the liver, and its role as an anti-cancer supplement is still controversial. Here, we evaluate the effects of methionine supplementation in liver cancer cells....
Article
Full-text available
Background: Rewiring of metabolism induced by oncogenic K-Ras in cancer cells involves both glucose and glutamine utilization sustaining enhanced, unrestricted growth. The development of effective anti-cancer treatments targeting metabolism may be facilitated by the identification and rational combinatorial targeting of metabolic pathways. Method...
Article
Full-text available
In breast cancer (BC) care, radiotherapy is considered an efficient treatment, prescribed both for controlling localized tumors or as a therapeutic option in case of inoperable, incompletely resected or recurrent tumors. However, approximately 90% of BC-related deaths are due to the metastatic tumor progression. Then, it is strongly desirable to im...
Article
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A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
Article
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Neuronal differentiation involves extensive modification of biochemical and morphological properties to meet novel functional requirements. Reorganization of the mitochondrial network to match the higher energy demand plays a pivotal role in this process. Mechanisms of neuronal differentiation in response to nerve growth factor (NGF) have been larg...
Article
Full-text available
Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor with poor survival. Cytoreduction in association with radiotherapy and temozolomide (TMZ) is the standard therapy, but response is heterogeneous and life expectancy is limited. The combined use of chemotherapeutic agents with drugs targeting cell metabolism is becoming an inte...
Article
Full-text available
The protein ataxin-3 carries a polyglutamine stretch close to the C-terminus that triggers a neurodegenerative disease in humans when its length exceeds a critical threshold. A role as a transcriptional regulator but also as a ubiquitin hydrolase has been proposed for this protein. Here, we report that, when expressed in the yeast Pichia pastoris,...
Article
The protein ataxin-3 (ATX3) triggers an amyloid-related neurodegenerative disease when its polyglutamine stretch is expanded beyond a critical threshold. We formerly demonstrated that the polyphenol epigallocatechin-3-gallate (EGCG) could redirect amyloid aggregation of a full-length, expanded ATX3 (ATX3-Q55) towards non-toxic, soluble, SDS-resista...
Article
Full-text available
Oncogenic K-ras is capable to control tumor growth and progression by rewiring cancer metabolism. In vitro NIH-Ras cells convert glucose to lactate and use glutamine to sustain anabolic processes, but their in vivo environmental adaptation and multiple metabolic pathways activation ability is poorly understood. Here, we show that NIH-Ras cancer cel...
Article
Epigallocatechin-3-gallate (EGCG) and tetracycline are two known inhibitors of amyloid aggregation able to counteract the fibrillation of most of the proteins involved in neurodegenerative diseases. We have recently investigated their effect on ataxin-3 (AT3), the polyglutamine-containing protein responsible for spinocerebellar ataxia type 3. We pr...
Article
Full-text available
Ataxin-3 (AT3) is a deubiquitinating enzyme that triggers an inherited neurodegenerative disorder, spinocerebellar ataxia type 3, when its polyglutamine (polyQ) stretch close to the C-terminus exceeds a critical length. AT3 variants carrying the expanded polyQ are prone to associate with each other into amyloid toxic aggregates, which are responsib...
Article
By combining NMR spectroscopy, transmission electron microscopy and circular dicroism we identified the structural determinants involved in the interaction of green tea catechins with Aβ1-42, PrP106-126 and ataxin-3 oligomers. Our data allow the elucidation of their mechanism of action, showing that the flavan-3-ol unit of catechins is essential fo...
Article
Full-text available
The polyglutamine (polyQ)-containing protein ataxin-3 (AT3) triggers the neurodegenerative disease spinocerebellar ataxia type 3 (SCA3) when its polyQ tract is expanded beyond a critical length. This results in protein aggregation and generation of toxic oligomers and fibrils. Currently, no effective treatment is available for such and other polyQ...
Article
Full-text available
Protein misfolding and aggregation in intracellular and extracellular spaces is regarded as a main marker of the presence of degenerative disorders such as amyloidoses. To elucidate the mechanisms of protein misfolding, the interaction of proteins with inorganic surfaces is of particular relevance, since surfaces displaying different wettability pr...
Data
Root Mean Square (RMS) fluctuations of JD protein. (A) in solution averaged in the 0–10 ns range (black) and in the 90–100 ns range (red), where the α2–α3 hairpin residues (light grey region in the RMS fluctuation graphs) show large fluctuations; (B) in contact with mica surface averaged in the 0–10 ns range (black) and in the 490–500 ns range (red...
Data
Root Mean Square Deviation (RMSD) of JD protein faced to gold surface (A) where two different stable regions are detectable, the first one from 25 to 450 ns and the second one from 500 to 700 ns. The first stable region is characterized by a hairpin domain fluctuating far from the globular core of the protein; the secondary structure of the hairpin...
Data
Detail of the time-dependent secondary structures evolution of the α2–α3 hairpin region (residues from 31 to 62) for the protein in solution (A), in contact with mica (B) and gold (C) surfaces. The presence of mica causes a change in the secondary structure from α-helices (blue) to coils (white), while the gold surface induces a two-step transition...
Data
Water contact angle on mica (A) and gold (B) surfaces. Panel (C) shows a SEM image of drop solution of JD after drying on gold surface. (TIFF)
Data
Aggregation kinetics of JD in solution monitored by FTIR spectroscopy and ThT fluorescence. (A) The second-derivative ATR/FTIR spectra in the amide I band of JD in solution are reported at different incubation times at 37°C. The second-derivative spectrum of the insoluble aggregates, obtained by sample centrifugation after 72 h of incubation (72 h...
Data
Mass spectrometry analysis of JD. ESI-MS spectra (A, C) and mass deconvolution (B, D) of JD before (A, B) and after (C, D) incubation. 19 µM protein in 5 mM ammonium acetate, 1% formic acid (A) or 7.5 µM in 2.5 mM ammonium acetate, 1% formic acid, 50% acetonitrile (C). The most intense peaks in panels A and C are labeled with the corresponding char...

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