LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 7 of total 7

Search options

  1. Article ; Online: Proteolysis at work: when time matters for a sensory organelle.

    Senatore, Emanuela / Feliciello, Antonio

    BioEssays : news and reviews in molecular, cellular and developmental biology

    2022  Volume 44, Issue 9, Page(s) e2200137

    MeSH term(s) Organelles/metabolism ; Proteasome Endopeptidase Complex/metabolism ; Proteolysis ; Ubiquitin/metabolism ; Ubiquitin-Protein Ligases/metabolism ; Ubiquitination
    Chemical Substances Ubiquitin ; Ubiquitin-Protein Ligases (EC 2.3.2.27) ; Proteasome Endopeptidase Complex (EC 3.4.25.1)
    Language English
    Publishing date 2022-07-25
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Comment
    ZDB-ID 50140-2
    ISSN 1521-1878 ; 0265-9247
    ISSN (online) 1521-1878
    ISSN 0265-9247
    DOI 10.1002/bies.202200137
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 2024: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  2. Article ; Online: Control of Mitochondrial Activity by the Ubiquitin Code in Health and Cancer.

    Rinaldi, Laura / Senatore, Emanuela / Iannucci, Rosa / Chiuso, Francesco / Feliciello, Antonio

    Cells

    2023  Volume 12, Issue 2

    Abstract: Cellular homeostasis is tightly connected to the broad variety of mitochondrial functions. To stay healthy, cells need a constant supply of nutrients, energy production and antioxidants defenses, undergoing programmed death when a serious, irreversible ... ...

    Abstract Cellular homeostasis is tightly connected to the broad variety of mitochondrial functions. To stay healthy, cells need a constant supply of nutrients, energy production and antioxidants defenses, undergoing programmed death when a serious, irreversible damage occurs. The key element of a functional integration of all these processes is the correct crosstalk between cell signaling and mitochondrial activities. Once this crosstalk is interrupted, the cell is not able to communicate its needs to mitochondria, resulting in oxidative stress and development of pathological conditions. Conversely, dysfunctional mitochondria may affect cell viability, even in the presence of nutrients supply and energy production, indicating the existence of feed-back control mechanisms between mitochondria and other cellular compartments. The ubiquitin proteasome system (UPS) is a multi-step biochemical pathway that, through the conjugation of ubiquitin moieties to specific protein substrates, controls cellular proteostasis and signaling, removing damaged or aged proteins that might otherwise accumulate and affect cell viability. In response to specific needs or changed extracellular microenvironment, the UPS modulates the turnover of mitochondrial proteins, thus influencing the organelle shape, dynamics and function. Alterations of the dynamic and reciprocal regulation between mitochondria and UPS underpin genetic and proliferative disorders. This review focuses on the mitochondrial metabolism and activities supervised by UPS and examines how deregulation of this control mechanism results in proliferative disorders and cancer.
    MeSH term(s) Humans ; Aged ; Ubiquitin/metabolism ; Mitochondria/metabolism ; Proteasome Endopeptidase Complex/metabolism ; Signal Transduction ; Mitochondrial Proteins/metabolism ; Neoplasms/metabolism ; Tumor Microenvironment
    Chemical Substances Ubiquitin ; Proteasome Endopeptidase Complex (EC 3.4.25.1) ; Mitochondrial Proteins
    Language English
    Publishing date 2023-01-05
    Publishing country Switzerland
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells12020234
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  3. Article: Pathophysiology of Primary Cilia: Signaling and Proteostasis Regulation.

    Senatore, Emanuela / Iannucci, Rosa / Chiuso, Francesco / Delle Donne, Rossella / Rinaldi, Laura / Feliciello, Antonio

    Frontiers in cell and developmental biology

    2022  Volume 10, Page(s) 833086

    Abstract: Primary cilia are microtubule-based, non-motile sensory organelles present in most types of growth-arrested eukaryotic cells. They are transduction hubs that receive and transmit external signals to the cells in order to control growth, differentiation ... ...

    Abstract Primary cilia are microtubule-based, non-motile sensory organelles present in most types of growth-arrested eukaryotic cells. They are transduction hubs that receive and transmit external signals to the cells in order to control growth, differentiation and development. Mutations of genes involved in the formation, maintenance or disassembly of ciliary structures cause a wide array of developmental genetic disorders, also known as ciliopathies. The primary cilium is formed during G1 in the cell cycle and disassembles at the G2/M transition. Following the completion of the cell division, the cilium reassembles in G1. This cycle is finely regulated at multiple levels. The ubiquitin-proteasome system (UPS) and the autophagy machinery, two main protein degradative systems in cells, play a fundamental role in cilium dynamics. Evidence indicate that UPS, autophagy and signaling pathways may act in synergy to control the ciliary homeostasis. However, the mechanisms involved and the links between these regulatory systems and cilium biogenesis, dynamics and signaling are not well defined yet. Here, we discuss the reciprocal regulation of signaling pathways and proteolytic machineries in the control of the assembly and disassembly of the primary cilium, and the impact of the derangement of these regulatory networks in human ciliopathies.
    Language English
    Publishing date 2022-05-11
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2737824-X
    ISSN 2296-634X
    ISSN 2296-634X
    DOI 10.3389/fcell.2022.833086
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  4. Article ; Online: Ubiquitylation of BBSome is required for ciliary assembly and signaling.

    Chiuso, Francesco / Delle Donne, Rossella / Giamundo, Giuliana / Rinaldi, Laura / Borzacchiello, Domenica / Moraca, Federica / Intartaglia, Daniela / Iannucci, Rosa / Senatore, Emanuela / Lignitto, Luca / Garbi, Corrado / Conflitti, Paolo / Catalanotti, Bruno / Conte, Ivan / Feliciello, Antonio

    EMBO reports

    2023  Volume 24, Issue 4, Page(s) e55571

    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 and regulators of the BBSome, an octameric ... ...

    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 and regulators of the BBSome, an octameric complex that controls the trafficking of cargos and receptors within the primary cilium. Although both structure and function of the BBSome have been extensively studied, the impact of ubiquitin signaling on BBSome is largely unknown. We identify the E3 ubiquitin ligase PJA2 as a novel resident of the ciliary compartment and regulator of the BBSome. Upon GPCR-cAMP stimulation, PJA2 ubiquitylates BBSome subunits. We demonstrate that ubiquitylation of BBS1 at lysine 143 increases the stability of the BBSome and promotes its binding to BBS3, an Arf-like GTPase protein controlling the targeting of the BBSome to the ciliary membrane. Downregulation of PJA2 or expression of a ubiquitylation-defective BBS1 mutant (BBS1
    MeSH term(s) Animals ; Cilia/metabolism ; Protein Transport ; Signal Transduction ; Bardet-Biedl Syndrome/genetics ; Receptors, G-Protein-Coupled/genetics ; Ubiquitination
    Chemical Substances Receptors, G-Protein-Coupled
    Language English
    Publishing date 2023-02-06
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2020896-0
    ISSN 1469-3178 ; 1469-221X
    ISSN (online) 1469-3178
    ISSN 1469-221X
    DOI 10.15252/embr.202255571
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 5433: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)
    Zs.MG 41: Show issues

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  5. Article ; Online: Downregulation of praja2 restrains endocytosis and boosts tyrosine kinase receptors in kidney cancer.

    Rinaldi, Laura / Chiuso, Francesco / Senatore, Emanuela / Borzacchiello, Domenica / Lignitto, Luca / Iannucci, Rosa / Donne, Rossella Delle / Fuggi, Mariano / Reale, Carla / Russo, Filomena / Russo, Nicola Antonino / Giurato, Giorgio / Rizzo, Francesca / Sellitto, Assunta / Santangelo, Michele / De Biase, Davide / Paciello, Orlando / D'Ambrosio, Chiara / Amente, Stefano /
    Garbi, Corrado / Dalla, Emiliano / Scaloni, Andrea / Weisz, Alessandro / Ambrosino, Concetta / Insabato, Luigi / Feliciello, Antonio

    Communications biology

    2024  Volume 7, Issue 1, Page(s) 208

    Abstract: Clear cell renal cell carcinoma (ccRCC) is the most common kidney cancer in the adult population. Late diagnosis, resistance to therapeutics and recurrence of metastatic lesions account for the highest mortality rate among kidney cancer patients. ... ...

    Abstract Clear cell renal cell carcinoma (ccRCC) is the most common kidney cancer in the adult population. Late diagnosis, resistance to therapeutics and recurrence of metastatic lesions account for the highest mortality rate among kidney cancer patients. Identifying novel biomarkers for early cancer detection and elucidating the mechanisms underlying ccRCC will provide clues to treat this aggressive malignant tumor. Here, we report that the ubiquitin ligase praja2 forms a complex with-and ubiquitylates the AP2 adapter complex, contributing to receptor endocytosis and clearance. In human RCC tissues and cells, downregulation of praja2 by oncogenic miRNAs (oncomiRs) and the proteasome markedly impairs endocytosis and clearance of the epidermal growth factor receptor (EGFR), and amplifies downstream mitogenic and proliferative signaling. Restoring praja2 levels in RCC cells downregulates EGFR, rewires cancer cell metabolism and ultimately inhibits tumor cell growth and metastasis. Accordingly, genetic ablation of praja2 in mice upregulates RTKs (i.e. EGFR and VEGFR) and induces epithelial and vascular alterations in the kidney tissue.In summary, our findings identify a regulatory loop between oncomiRs and the ubiquitin proteasome system that finely controls RTKs endocytosis and clearance, positively impacting mitogenic signaling and kidney cancer growth.
    MeSH term(s) Adult ; Animals ; Humans ; Mice ; Carcinoma, Renal Cell/genetics ; Carcinoma, Renal Cell/pathology ; Down-Regulation ; Endocytosis ; ErbB Receptors/genetics ; ErbB Receptors/metabolism ; Kidney Neoplasms/genetics ; Kidney Neoplasms/pathology ; Proteasome Endopeptidase Complex/metabolism ; Receptor Protein-Tyrosine Kinases/genetics ; Ubiquitin/metabolism
    Chemical Substances ErbB Receptors (EC 2.7.10.1) ; Proteasome Endopeptidase Complex (EC 3.4.25.1) ; Receptor Protein-Tyrosine Kinases (EC 2.7.10.1) ; Ubiquitin ; PJA2 protein, human (EC 2.3.2.27) ; PJA2 protein, mouse (EC 2.3.2.27)
    Language English
    Publishing date 2024-02-20
    Publishing country England
    Document type Journal Article
    ISSN 2399-3642
    ISSN (online) 2399-3642
    DOI 10.1038/s42003-024-05823-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  6. Article ; Online: Targeted inhibition of ubiquitin signaling reverses metabolic reprogramming and suppresses glioblastoma growth.

    Delle Donne, Rossella / Iannucci, Rosa / Rinaldi, Laura / Roberto, Luca / Oliva, Maria A / Senatore, Emanuela / Borzacchiello, Domenica / Lignitto, Luca / Giurato, Giorgio / Rizzo, Francesca / Sellitto, Assunta / Chiuso, Francesco / Castaldo, Salvatore / Scala, Giovanni / Campani, Virginia / Nele, Valeria / De Rosa, Giuseppe / D'Ambrosio, Chiara / Garbi, Corrado /
    Scaloni, Andrea / Weisz, Alessandro / Ambrosino, Concetta / Arcella, Antonella / Feliciello, Antonio

    Communications biology

    2022  Volume 5, Issue 1, Page(s) 780

    Abstract: Glioblastoma multiforme (GBM) is the most frequent and aggressive form of primary brain tumor in the adult population; its high recurrence rate and resistance to current therapeutics urgently demand a better therapy. Regulation of protein stability by ... ...

    Abstract Glioblastoma multiforme (GBM) is the most frequent and aggressive form of primary brain tumor in the adult population; its high recurrence rate and resistance to current therapeutics urgently demand a better therapy. Regulation of protein stability by the ubiquitin proteasome system (UPS) represents an important control mechanism of cell growth. UPS deregulation is mechanistically linked to the development and progression of a variety of human cancers, including GBM. Thus, the UPS represents a potentially valuable target for GBM treatment. Using an integrated approach that includes proteomics, transcriptomics and metabolic profiling, we identify praja2, a RING E3 ubiquitin ligase, as the key component of a signaling network that regulates GBM cell growth and metabolism. Praja2 is preferentially expressed in primary GBM lesions expressing the wild-type isocitrate dehydrogenase 1 gene (IDH1). Mechanistically, we found that praja2 ubiquitylates and degrades the kinase suppressor of Ras 2 (KSR2). As a consequence, praja2 restrains the activity of downstream AMP-dependent protein kinase in GBM cells and attenuates the oxidative metabolism. Delivery in the brain of siRNA targeting praja2 by transferrin-targeted self-assembling nanoparticles (SANPs) prevented KSR2 degradation and inhibited GBM growth, reducing the size of the tumor and prolonging the survival rate of treated mice. These data identify praja2 as an essential regulator of cancer cell metabolism, and as a potential therapeutic target to suppress GBM growth.
    MeSH term(s) Adult ; Animals ; Brain Neoplasms/genetics ; Brain Neoplasms/pathology ; Cell Line, Tumor ; Glioblastoma/metabolism ; Humans ; Mice ; Proteasome Endopeptidase Complex/metabolism ; Signal Transduction ; Ubiquitin
    Chemical Substances Ubiquitin ; Proteasome Endopeptidase Complex (EC 3.4.25.1)
    Language English
    Publishing date 2022-08-02
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 2399-3642
    ISSN (online) 2399-3642
    DOI 10.1038/s42003-022-03639-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  7. Article ; Online: The TBC1D31/praja2 complex controls primary ciliogenesis through PKA-directed OFD1 ubiquitylation.

    Senatore, Emanuela / Chiuso, Francesco / Rinaldi, Laura / Intartaglia, Daniela / Delle Donne, Rossella / Pedone, Emilia / Catalanotti, Bruno / Pirone, Luciano / Fiorillo, Bianca / Moraca, Federica / Giamundo, Giuliana / Scala, Giovanni / Raffeiner, Andrea / Torres-Quesada, Omar / Stefan, Eduard / Kwiatkowski, Marcel / van Pijkeren, Alienke / Morleo, Manuela / Franco, Brunella /
    Garbi, Corrado / Conte, Ivan / Feliciello, Antonio

    The EMBO journal

    2021  Volume 40, Issue 10, Page(s) e106503

    Abstract: The primary cilium is a microtubule-based sensory organelle that dynamically links signalling pathways to cell differentiation, growth, and development. Genetic defects of primary cilia are responsible for genetic disorders known as ciliopathies. ... ...

    Abstract The primary cilium is a microtubule-based sensory organelle that dynamically links signalling pathways to cell differentiation, growth, and development. Genetic defects of primary cilia are responsible for genetic disorders known as ciliopathies. Orofacial digital type I syndrome (OFDI) is an X-linked congenital ciliopathy caused by mutations in the OFD1 gene and characterized by malformations of the face, oral cavity, digits and, in the majority of cases, polycystic kidney disease. OFD1 plays a key role in cilium biogenesis. However, the impact of signalling pathways and the role of the ubiquitin-proteasome system (UPS) in the control of OFD1 stability remain unknown. Here, we identify a novel complex assembled at centrosomes by TBC1D31, including the E3 ubiquitin ligase praja2, protein kinase A (PKA), and OFD1. We show that TBC1D31 is essential for ciliogenesis. Mechanistically, upon G-protein-coupled receptor (GPCR)-cAMP stimulation, PKA phosphorylates OFD1 at ser735, thus promoting OFD1 proteolysis through the praja2-UPS circuitry. This pathway is essential for ciliogenesis. In addition, a non-phosphorylatable OFD1 mutant dramatically affects cilium morphology and dynamics. Consistent with a role of the TBC1D31/praja2/OFD1 axis in ciliogenesis, alteration of this molecular network impairs ciliogenesis in vivo in Medaka fish, resulting in developmental defects. Our findings reveal a multifunctional transduction unit at the centrosome that links GPCR signalling to ubiquitylation and proteolysis of the ciliopathy protein OFD1, with important implications on cilium biology and development. Derangement of this control mechanism may underpin human genetic disorders.
    MeSH term(s) Animals ; Cyclic AMP-Dependent Protein Kinases/genetics ; Cyclic AMP-Dependent Protein Kinases/metabolism ; Humans ; Oryzias ; Signal Transduction/genetics ; Signal Transduction/physiology ; Two-Hybrid System Techniques ; Ubiquitin/genetics ; Ubiquitin/metabolism ; Ubiquitin-Protein Ligases/genetics ; Ubiquitin-Protein Ligases/metabolism ; Ubiquitination
    Chemical Substances Ubiquitin ; PJA2 protein, human (EC 2.3.2.27) ; Ubiquitin-Protein Ligases (EC 2.3.2.27) ; Cyclic AMP-Dependent Protein Kinases (EC 2.7.11.11)
    Language English
    Publishing date 2021-05-02
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 586044-1
    ISSN 1460-2075 ; 0261-4189
    ISSN (online) 1460-2075
    ISSN 0261-4189
    DOI 10.15252/embj.2020106503
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 1808: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)
    Zs.MG 100: Show issues

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

To top