A5072100926- Cancer Cells and Metastasis
- Cell death mechanisms and regulation
- Thyroid Cancer Diagnosis and Treatment
- Epigenetics and DNA Methylation
- Ubiquitin and proteasome pathways
- BRCA gene mutations in cancer
- Nutrition, Genetics, and Disease
- Cell Adhesion Molecules Research
- Endoplasmic Reticulum Stress and Disease
- Cancer-related Molecular Pathways
- Cytokine Signaling Pathways and Interactions
- RNA Interference and Gene Delivery
- Cancer-related gene regulation
- Mitochondrial Function and Pathology
- RNA modifications and cancer
- Protein Kinase Regulation and GTPase Signaling
- Protease and Inhibitor Mechanisms
- Wnt/β-catenin signaling in development and cancer
- Protein Tyrosine Phosphatases
- Thyroid Disorders and Treatments
- ATP Synthase and ATPases Research
- S100 Proteins and Annexins
- Growth Hormone and Insulin-like Growth Factors
- RNA Research and Splicing
- interferon and immune responses
Federico II University Hospital
2003-2024
University of Naples Federico II
2008-2023
Ceinge Biotecnologie Avanzate (Italy)
2016-2020
Istituto Neurologico Mediterraneo
2018
University Hospital of Bern
2018
University of Bern
2018
University of Salerno
2018
Institute of Protein Biochemistry
2018
National Academies of Sciences, Engineering, and Medicine
2018
Karolinska Institutet
2018
Here, we show that the anaplastic thyroid carcinoma (ATC) features up-regulation of a set genes involved in control cell cycle progression and chromosome segregation. This phenotype differentiates ATC from normal tissue well-differentiated papillary carcinoma. Transcriptional promoters up-regulated are characterized by modular organization featuring binding sites for E2F NF-Y transcription factors cycle-dependent element (CDE)/cell gene homology region (CHR) cis-regulatory elements. Two...
TRAP1, a mitochondrial chaperone (Hsp75) with antioxidant and antiapoptotic functions, is involved in multidrug resistance human colorectal carcinoma cells. Through proteomic analysis of TRAP1 coimmunoprecipitation complexes, the Ca(2+)-binding protein Sorcin was identified as new interactor. This result prompted us to investigate presence role mitochondria from colon Using fluorescence microscopy Western blot purified submitochondrial fractions, we showed localization an isoform...
Abstract Context: A substantial proportion of athyreotic levothyroxine (LT4)-treated patients experience hypothyroid-like symptoms. During LT4 replacement, levels the active hormone triiodothyronine (T3) strictly depend on type 2-deiodinase (D2)-mediated activation LT4. The Thr92Ala polymorphism and 258 G/A in DIO2 gene have been associated with various clinical conditions. Objectives: To investigate effects polymorphisms thyroid homeostasis. Design: We compared presurgical hormonal status...
Human glioblastoma is the most frequent and aggressive form of brain tumour in adult population. Proteolytic turnover suppressors by ubiquitin–proteasome system a mechanism that cells can adopt to sustain their growth invasiveness. However, identity targets regulators are still unknown. Here we report RING ligase praja2 ubiquitylates degrades Mob, core component NDR/LATS kinase positive regulator tumour-suppressor Hippo cascade. Degradation Mob through attenuates cascade sustains vivo....
AKAP121 focuses distinct signaling events from membrane to mitochondria by binding and targeting cAMP-dependent protein kinase (PKA), tyrosine phosphatase (PTPD1), mRNA. We find that also targets src via PTPD1. increased src-dependent phosphorylation of mitochondrial substrates enhanced the activity cytochrome c oxidase, a component respiratory chain. Mitochondrial potential ATP oxidative synthesis were in an src- PKA-dependent manner. Finally, siRNA-mediated silencing endogenous drastically...
Conditions perturbing the homeostasis of endoplasmic reticulum (ER) cause accumulation unfolded proteins and trigger ER stress. In PC Cl3 thyroid cells, thapsigargin tunicamycin interfered with folding thyroglobulin, causing this very large secretory glycoprotein in ER. Consequently, mRNAs encoding BiP XBP-1 were induced spliced, respectively. absence apoptosis, differentiation cells was inhibited. mRNA protein levels thyroid-specific genes thyroperoxidase sodium/iodide symporter...
Abstract Bardet‐Biedl syndrome (BBS) is a ciliopathy characterized by retinal degeneration, obesity, renal abnormalities, postaxial polydactyly, and developmental defects. Genes mutated in BBS encode for components regulators of the BBSome, an octameric complex that controls trafficking cargos receptors within primary cilium. Although both structure function BBSome have been extensively studied, impact ubiquitin signaling on largely unknown. We identify E3 ligase PJA2 as novel resident...
AbstractA-kinase anchor protein 121 (AKAP121) and its spliced isoform AKAP84 kinase A (PKA) to the outer membrane of mitochondria, focusing enhancing cyclic AMP signal transduction organelle. We find that AKAP121/84 also binds PTPD1, a src-associated tyrosine phosphatase. signaling complex containing AKAP121, PKA, src is assembled in vivo. PTPD1 activates increases magnitude duration epidermal growth factor (EGF) signaling. EGF receptor phosphorylation downstream activation ERK 1/2...
PTPD1 is a cytosolic nonreceptor tyrosine phosphatase and positive regulator of the Src-epidermal growth factor transduction pathway. We show that localizes along actin filaments at adhesion plaques. forms stable complex via distinct molecular modules with actin, Src kinase, focal kinase (FAK), scaffold protein enriched Overexpression promoted cell scattering migration, short hairpin RNA-mediated silencing endogenous PTPD1, or expression mutants lacking either catalytic activity...
Mitochondria are the powerhouses of energy production and sites where metabolic pathway survival signals integrate focus, promoting adaptive responses to hormone stimulation nutrient availability. Increasing evidence suggests that mitochondrial bioenergetics, metabolism signaling linked tumorigenesis. AKAP1 scaffolding protein integrates cAMP src on mitochondria, regulating organelle biogenesis, oxidative cell survival. Here, we provide is a transcriptional target Myc supports growth cancer...
The aim of the present study was to determine function and role scaffold protein AKAP121, tethering cAMP dependent kinase A outer wall mitochondria, in neonatal ventricular myocytes heart.Competitive peptides displacing AKAP121 from mitochondria tissue cells were used investigate mitochondrial function, reactive oxygen species (ROS) generation, cell survival. Displacement by synthetic triggers death program cardiomyocytes. Under pathological conditions vivo, a rat model cardiac hypertrophy...
Abstract The primary cilium emanates from the cell surface of growth-arrested cells and plays a central role in vertebrate development tissue homeostasis. mechanisms that control ciliogenesis have been extensively explored. However, intersection between GPCR signaling ubiquitin pathway stability are unknown. Here we observe cAMP elevation promotes cilia resorption. At centriolar satellites, identify multimeric complex nucleated by PCM1 includes two kinases, NEK10 PKA, E3 ligase CHIP. We show...
MitoAKAPs (mitochondrial A kinase anchoring proteins), encoded by the Akap1 gene, regulate multiple cellular processes governing mitochondrial homeostasis and cell viability. Although alterations have been associated to endothelial dysfunction, role of mitoAKAPs in vasculature is currently unknown. To test this, postischemic neovascularization, vascular function, arterial blood pressure were analyzed knockout mice (Akap1-/- ) their wild-type (wt) littermates. Primary cultures aortic cells...
Abstract Activation of G-protein coupled receptors elevates cAMP levels promoting dissociation protein kinase A (PKA) holoenzymes and release catalytic subunits (PKAc). This results in PKAc-mediated phosphorylation compartmentalized substrates that control central aspects cell physiology. The mechanism PKAc activation signaling have been largely characterized. However, the modes inactivation by regulated proteolysis were unknown. Here, we identify a regulatory precisely tunes stability...
Ras proteins are membrane-associated transducers of eternal stimuli to unknown intracellular targets. The constitutively activated v-ras oncogene induces dedifferentiation in thyroid cells. v-Ras appears act by stimulating protein kinase C (PKC), which inhibits the nuclear migration catalytic subunit cAMP-dependent A (PKA). Nuclear tissue-specific and housekeeping trans-acting factors that dependent on phosphorylation PKA thus inactivated. Exclusion from nucleus could represent a general...
Friedreich's ataxia is a recessive neurodegenerative disease due to insufficient expression of the mitochondrial protein frataxin. Although it has been shown that frataxin involved in control intracellular iron metabolism, by interfering with biosynthesis proteins iron/sulphur (Fe/S) clusters its role not well established. We studied and mRNA localisation during cellular differentiation. used human colon adenocarcinoma cell line Caco-2, as considered good model for intestinal epithelial...
PTPD1, a cytosolic non-receptor protein-tyrosine phosphatase, stimulates the Src-EGF transduction pathway. Localization of PTPD1 at actin cytoskeleton and adhesion sites is required for cell scattering migration. Here, we show that during EGF stimulation, rapidly recruited to endocytic vesicles containing receptor. Endosomal localization mediated by interaction with KIF16B, an endosomal kinesin modulates receptor recycling plasma membrane. Silencing promotes degradation inhibits downstream...
Carbonic anhydrase IX (CA IX) is a transmembrane protein affecting pH regulation, cell migration/invasion, and survival in hypoxic tumors. Although the pathways related to CA have begun emerge, molecular partners mediating its functions remain largely unknown. Here we characterize interactome HEK-293 cells. Most of identified IX-binding contain HEAT/ARM repeat domain belong nuclear transport machinery. We show that interaction with two these proteins, namely XPO1 exportin TNPO1 importin,...