- Cell death mechanisms and regulation
- DNA Repair Mechanisms
- Cancer-related Molecular Pathways
- Caveolin-1 and cellular processes
- Multiple Myeloma Research and Treatments
- Chronic Myeloid Leukemia Treatments
- Protein Kinase Regulation and GTPase Signaling
- Autophagy in Disease and Therapy
- Ubiquitin and proteasome pathways
- Peptidase Inhibition and Analysis
- Quinazolinone synthesis and applications
- PARP inhibition in cancer therapy
- HIV/AIDS drug development and treatment
- PI3K/AKT/mTOR signaling in cancer
- Microtubule and mitosis dynamics
- Retinoids in leukemia and cellular processes
- Protein Degradation and Inhibitors
- Hippo pathway signaling and YAP/TAZ
- Ferroptosis and cancer prognosis
- ATP Synthase and ATPases Research
- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- Genetics, Aging, and Longevity in Model Organisms
- Epigenetics and DNA Methylation
- Cancer, Hypoxia, and Metabolism
University of Rome Tor Vergata
2014-2023
Fondazione Santa Lucia
2013-2023
Dulbecco Telethon Institute
2003-2023
European University of Rome
2023
Istituti di Ricovero e Cura a Carattere Scientifico
2010-2022
Centro de Investigación del Cáncer
2012
Dana-Farber Cancer Institute
2007
European Bioinformatics Institute
2002
European Molecular Biology Laboratory
1998-2000
European Molecular Biology Laboratory
2000
Caspase-8 is a proapoptotic protease that suppresses neuroblastoma metastasis by inducing programmed cell death. Paradoxically, caspase-8 can also promote migration among nonapoptotic cells; here, we show when apoptosis compromised. Migration enhanced recruitment to the cellular machinery following integrin ligation. catalytic activity not required for caspase-8-enhanced migration; rather, interacts with multiprotein complex include focal adhesion kinase and calpain 2 (CPN2), enhancing...
Abstract Background Mutations in the DNA damage response (DDR) factors, breast cancer 1 (BRCA1) and BRCA2, sensitize tumor cells to poly(ADP-ribose) polymerase (PARP) inhibitors. The ataxia telangiectasia mutated (ATM) kinase is a key DDR protein whose heterozygous germline mutation moderate–risk factor for developing cancer. In this study, we examined whether ATM inactivation cell lines confers sensitivity PARP Methods Wild-type BRCA1/2 ( i.e. , MCF-7 ZR-75-1 lines) were genetically...
Caspase 8 is a critical upstream initiator of programmed cell death but, paradoxically, has also been shown to promote migration. Here, we show that tyrosine 380 in the linker loop human caspase switch determining function. Our studies that, addition its cytosolic distribution, recruited lamella migrating cells. Although catalytic domain sufficient for recruitment and promotion migration, activity <i>per se</i> not required. Instead, find integrin-mediated adhesion promotes phosphorylation...
Caspase-8 is a key player in extrinsic apoptosis and its activity often downregulated cancer. However, human expression retained some tumors, including glioblastoma (GBM), suggesting that it may support cancer growth these contexts. GBM, the most aggressive of gliomas, characterized by extensive angiogenesis an inflammatory microenvironment development resistance to therapies. We have recently shown sustains neoplastic transformation vitro GBM cell lines. Here, we demonstrate Caspase-8,...
ATM kinase preserves genomic stability by acting as a tumour suppressor. However, its identification component of several signalling networks suggests dualism for in cancer. Here we report that expression and activity promotes HER2-dependent tumorigenicity vitro vivo. We reveal correlation between activation the reduced time to recurrence patients diagnosed with invasive HER2-positive breast Furthermore, identify novel modulator HER2 protein acts promoting complex chaperone HSP90, therefore...
Article27 November 2020Open Access Source DataTransparent process Redox activation of ATM enhances GSNOR translation to sustain mitophagy and tolerance oxidative stress Claudia Cirotti orcid.org/0000-0001-6267-8034 Department Biology, Tor Vergata University, Rome, Italy Laboratory Cell Signaling, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Fondazione Santa Lucia, ItalyThese authors contributed equally this work Search for more papers by author Salvatore Rizza...
// Martina Antonelli 1, 2 , Flavie Strappazzon 1 Ivan Arisi 3 Rossella Brandi Mara D'Onofrio Manolo Sambucci 4 Gwenola Manic Ilio Vitale 2, 5 Daniela Barilà Venturina Stagni Instituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Fondazione Santa Lucia, Rome, Italy Department of Biology, University Rome 'Tor Vergata', Genomics Facility, European Brain Research Institute (EBRI) 'Rita Levi-Montalcini', Neuroimmunology Unit, IRCCS, Regina Elena National Cancer Center Institute,...
A search for novel genes that are up-regulated during development and differentiation of the epithelial cells intestinal mucosa led us to isolation Dri 42 cDNA clone (Dri, differentially expressed in rat intestine). The nucleotide sequence full-length has shown it encodes a 35.5-kDa protein with one consensus N-linked glycosylation alternating hydrophilic hydrophobic domains. To determine intracellular localization we have raised polyclonal antibodies hens against bacterially produced...
The nonreceptor tyrosine kinase c-Abl may contribute to the regulation of apoptosis. activity is induced in nucleus upon DNA damage, and its activation required for execution apoptotic program. Recently, nuclear during death receptor-induced apoptosis has been reported; however, mechanism remains largely obscure. Here we show that cleaved by caspases tumor necrosis factor- Fas Cleavage at very C-terminal region occurs mainly cytoplasmic compartment generates a 120-kDa fragment lacks export...
Abstract Here we show the antimyeloma cytotoxicity of adaphostin and carried out expression profiling adaphostin-treated multiple myeloma (MM) cells to identify its molecular targets. Surprisingly, c-Jun was most up-regulated gene even at earliest point analysis (2 h). We also observed adaphostin-induced c-Abl cleavage in immunoblot analysis. Proteasome inhibitor bortezomib, but not melphalan or dexamethasone, induced similar effects, indicating unique agent-dependent mechanisms. Using...
Caspase 8 is a cysteine protease that initiates apoptotic signaling via the extrinsic pathway in manner dependent upon association with early endosomes. Previously, we identified caspase as an effector of migration, promoting motility phosphorylation on Tyr-380 by Src family kinases and its subsequent homology 2 domain-containing proteins. Here demonstrate regulation small GTPase Rab5, which mediates endosome formation, homotypic fusion, maturation 8. Regulation requires site but not...
Abstract Functionally distinct T-helper (Th) subsets orchestrate immune responses. Maintenance of homeostasis through the tight control inflammatory Th cells is crucial to avoid autoimmune inflammation. Activation-Induced Cell Death (AICD) regulates T cells, and it has never been investigated in human cells. We generated stable clones involved diseases, such as Th1, Th17 Th1/17 from healthy donors (HD) multiple sclerosis (MS) patients we measured AICD. find that Th1 are sensitive, whereas...
Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) has been proposed as a potent tool to trigger apoptosis in cancer therapy. However, since ∼60% of tumour cell lines and most primary cancers are resistant TRAIL-induced apoptosis, several combined therapy approaches aimed sensitize cells TRAIL have developed. One the major targets these cFLIP proteins they interfere with initiation induction by TRAIL, over-expressed many their down-regulation enhances sensitivity. Although,...