A5012691987- Hedgehog Signaling Pathway Studies
- Epigenetics and DNA Methylation
- Cancer-related Molecular Pathways
- Neuroblastoma Research and Treatments
- Immune Cell Function and Interaction
- Chromatin Remodeling and Cancer
- Glioma Diagnosis and Treatment
- Ubiquitin and proteasome pathways
- Genomics and Chromatin Dynamics
- Microtubule and mitosis dynamics
- Cancer, Hypoxia, and Metabolism
- MicroRNA in disease regulation
- Oral and Maxillofacial Pathology
- interferon and immune responses
- RNA modifications and cancer
- Ocular Disorders and Treatments
- Genetics and Neurodevelopmental Disorders
- Protein Degradation and Inhibitors
- Polyamine Metabolism and Applications
- Cancer Genomics and Diagnostics
- Histone Deacetylase Inhibitors Research
- Myasthenia Gravis and Thymoma
- Neurogenetic and Muscular Disorders Research
- Colorectal Cancer Treatments and Studies
- Monoclonal and Polyclonal Antibodies Research
Sapienza University of Rome
2010-2024
Italian Institute of Technology
2013-2023
Center for Life Sciences
2015
Center for NanoScience
2014
The University of Texas Health Science Center at San Antonio
1984-1996
The University of Texas at San Antonio
1996
Stanford University
1982
Fred Hutch Cancer Center
1982
WinnMed
1979
Article4 December 2014Open Access Source Data Gli1/DNA interaction is a druggable target for Hedgehog-dependent tumors Paola Infante Center Life [email protected], Istituto Italiano di Tecnologia, Rome, Italy Search more papers by this author Mattia Mori Romina Alfonsi Department of Molecular Medicine, University La Sapienza, Francesca Ghirga Dipartimento Chimica e Tecnologie del Farmaco, Federica Aiello Chemistry and Industrial Chemistry, Pisa, Sara Toscano Cinzia Ingallina Mariangela Siler...
Medulloblastoma is the most common pediatric malignant brain tumor, arising from aberrant cerebellar precursors' development, a process mainly controlled by Hedgehog (Hh) signaling pathway. Histone deacetylase HDAC1 has been recently shown to modulate Hh signaling, deacetylating its effectors Gli1/2 and enhancing their transcriptional activity. Therefore, HDAC may represent potential therapeutic target for Hh-dependent tumors, but still little information available on physiological...
ABSTRACT Eukaryotic Translation Initiation Factor 5A (EIF5A) is a translation factor regulated by hypusination, unique posttranslational modification catalyzed deoxyhypusine synthetase (DHPS) and hydroxylase (DOHH) starting from the polyamine spermidine. Emerging data are showing that hypusinated EIF5A regulates key cellular processes such as autophagy, senescence, homeostasis, energy metabolism, plays role in cancer. However, effects of inhibition preclinical cancer models, mechanism...
Glioblastoma multiforme (GB) is the most malignant primary brain tumor in humans, with an overall survival of approximatively 15 months. The molecular heterogeneity GB, as well its rapid progression, invasiveness and occurrence drug-resistant cancer stem cells, limits efficacy current treatments. In order to develop innovative therapeutic strategy, it mandatory identify characterize new players responsible for GB phenotype. this study, RNA-binding ubiquitin ligase MEX3A was selected from a...
The morphogenic Hedgehog (Hh) signaling regulates postnatal cerebellar development and its aberrant activation leads to medulloblastoma. transcription factors Gli1 Gli2 are the activators of Hh pathway their function is finely controlled by different covalent modifications, such as phosphorylation ubiquitination. We show here that endogenously acetylated this modification represents a key regulatory step for signaling. histone acetyltransferase (HAT) coactivator p300, but not other HATs,...
Aberrant Sonic Hedgehog/Gli (Hh/Gli) signaling pathway is a critical regulator of hedgehog medulloblastoma (SHH-MB). Cancer stem cells (CSCs), thought to be largely responsible for tumor initiation, maintenance, dissemination and relapse, have been identified in SHH-MB. Since we previously demonstrated that Hh/Gli controls CSCs features SHH-MB these tumors miR-326 down regulated, here investigated whether there functional link between miR-326. We evaluated β-arrestin1 (Arrb1) its intragenic...
Article27 May 2016Open Access Source DataTransparent process SCF (Fbxl17) ubiquitylation of Sufu regulates Hedgehog signaling and medulloblastoma development Madalina Raducu Cancer Research UK Medical Council Institute for Radiation Oncology, Department University Oxford, Search more papers by this author Ella Fung Sébastien Serres Paola Infante Center Life [email protected], Istituto Italiano di Tecnologia, Rome, Italy Alessandro Barberis Roman Fischer Target Discovery Institute, Nuffield...
Abstract Hedgehog (Hh) inhibitors have emerged as valid tools in the treatment of a wide range cancers. Indeed, aberrant activation Hh pathway occurring either by ligand-dependent or -independent mechanisms is key driver tumorigenesis. The smoothened (Smo) receptor one main upstream transducers signaling and validated target for development anticancer compounds, underlined FDA-approved Smo antagonist Vismodegib (GDC-0449/Erivedge) basal cell carcinoma. However, mutations that confer...
Suppressor of Fused (SuFu), a tumour suppressor mutated in medulloblastoma, is central player Hh signalling, pathway crucial for development and deregulated cancer. Although the control Gli transcription factors by SuFu critical our understanding mechanism regulating this key event remains limited. Here, we show that Itch/β-arrestin2 complex binds induces its Lys63-linked polyubiquitylation without affecting stability. This process increases association with Gli3, promoting conversion Gli3...
This work aims at elucidating the mechanism and kinetics of hydrolysis GANT61, first most-widely used inhibitor Hedgehog (Hh) signalling pathway that targets Glioma-associated oncogene homologue (Gli) proteins, confirming chemical nature its bioactive form. GANT61 is poorly stable under physiological conditions rapidly hydrolyses into an aldehyde species (GANT61-A), which devoid biological activity against Hh signalling, a diamine derivative (GANT61-D), has shown inhibition Gli-mediated...
Abstract The Hedgehog (Hh) pathway is essential for embryonic development and tissue homeostasis. Aberrant Hh signaling may occur in a wide range of human cancers, such as medulloblastoma, the most common brain malignancy childhood. Here, we identify endoplasmic reticulum aminopeptidase 1 (ERAP1), key regulator innate adaptive antitumor immune responses, previously unknown player pathway. We demonstrate that ERAP1 binds deubiquitylase enzyme USP47, displaces USP47-associated βTrCP,...
Highlights•Therapeutic doses of phenformin suppress Hedgehog-dependent tumor growth•Phenformin inhibits mGPD in cancer cells but does not affect complex I activity•Inhibition mimics and increases redox state/NADH content•Elevated NADH promotes Gli1/CtBP2 formation inhibition growthSummaryThe antidiabetic drug displays potent anticancer activity different tumors, its mechanism action remains elusive. Using Shh medulloblastoma as model, we show here that at clinically relevant concentrations,...
: Pharmacological Hedgehog (Hh) pathway inhibition has emerged as a valuable anticancer strategy. A number of small molecules able to block the at upstream receptor Smoothened (Smo) or downstream effector glioma-associated oncogene 1 (Gli1) been designed and developed. In recent study, we exploited high versatility natural isoflavone scaffold for targeting Hh signaling multiple levels showing that simultaneous Smo Gli1 provided synergistic stronger than single administration. This approach...
Alloreactive T cell clones with distinct specificities were used to raise anti-idiotypic antisera via an F1 anti-(parent anti-F1) protocol. Antisera raised that could stimulate the proliferation of appropriate clone, but not other clones. The active fraction for was immunoglobulin. In addition proliferation, antiserum induce clone secrete substantial amounts interleukin 2 (IL-2). Production IL-2 appeared independent involvement accessory cells. These cells may be unnecessary production in...
Abstract MRE11 is a component of the MRE11/RAD50/NBS1 (MRN) complex, whose activity essential to control faithful DNA replication and prevent accumulation deleterious double-strand breaks. In humans, hypomorphic mutations in these genes lead damage response (DDR)-defective cancer-prone syndromes. Moreover, MRN complex dysfunction dramatically affects nervous system, where required restrain MYCN-dependent stress, during rapid expansion progenitor cells. MYCN activation, often due genetic...