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APEH Inhibition Affects Osteosarcoma Cell Viability via Downregulation of the Proteasome (74 visite)

Palumbo R, Gogliettino M, Cocca E, Iannitti R, Sandomenico A, Ruvo M, Balestrieri M, Rossi M, Palmieri G

Int J Mol Sc (ISSN: 1422-0067electronic, 1422-0067linking, 1661-6596), 2016 Sep 23; 17(10): N/D-N/D.

Tipo di articolo: Journal Article,

Impact factor: 3.226

Impact factor a 5 anni: 3.482


Parole chiave: Acylpeptide Hydrolase (apeh), Anti-Tumoral Target, Osteosarcoma Cell Lines, Peptide Inhibitor, Proteasome,

Url: Non disponibile.

The proteasome is a multienzymatic complex that controls the half-life of the majority of intracellular proteins, including those involved in apoptosis and cell-cycle progression. Recently, proteasome inhibition has been shown to be an effective anticancer strategy, although its downregulation is often accompanied by severe undesired side effects. We previously reported that the inhibition of acylpeptide hydrolase (APEH) by the peptide SsCEI 4 can significantly affect the proteasome activity in A375 melanoma or Caco-2 adenocarcinoma cell lines, thus shedding new light on therapeutic strategies based on downstream regulation of proteasome functions. In this work, we investigated the functional correlation between APEH and proteasome in a panel of cancer cell lines, and evaluated the cell proliferation upon SsCEI 4-treatments. Results revealed that SsCEI 4 triggered a proliferative arrest specifically in osteosarcoma U2OS cells via downregulation of the APEH-proteasome system, with the accumulation of the typical hallmarks of proteasome: NF-kappaB, p21(Waf1), and polyubiquitinylated proteins. We found that the SsCEI 4 anti-proliferative effect involved a senescence-like growth arrest without noticeable cytotoxicity. These findings represent an important step toward understanding the mechanism(s) underlying the APEH-mediated downregulation of proteasome in order to design new molecules able to efficiently regulate the proteasome system for alternative therapeutic strategies.
*** IBB - CNR ***

Institute of Biostructure and Bioimaging, National Research Council (CNR-IBB), Napoli 80134, Italy. rosanna.palumbo@cnr.it., Institute of Biosciences and BioResources, National Research Council (CNR-IBBR), Napoli 80131, Italy. marta.gogliettino@ibbr.cnr.it., Institute of Biosciences and BioResources, National Research Council (CNR-IBBR), Napoli 80131, Italy. ennio.cocca@ibbr.cnr.it., Institute of Biostructure and Bioimaging, National Research Council (CNR-IBB), Napoli 80134, Italy. robertaiannitti@gmail.com., Institute of Biostructure and Bioimaging, National Research Council (CNR-IBB), Napoli 80134, Italy. annamaria.sandomenico@gmail.com., Institute of Biostructure and Bioimaging, National Research Council (CNR-IBB), Napoli 80134, Italy. menotti.ruvo@unina.it., Institute of Biosciences and BioResources, National Research Council (CNR-IBBR), Napoli 80131, Italy. marco.balestrieri@ibbr.cnr.it., Institute of Biosciences and BioResources, National Research Council (CNR-IBBR), Napoli 80131, Italy. mose.rossi@ibbr.cnr.it., Institute of Biosciences and BioResources, National Research Council (CNR-IBBR), Napoli 80131, Italy. gianna.palmieri@ibbr.cnr.it.,
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[Pulisci modulo]
Mercurio FA, Di Natale C, Pirone L, Iannitti R, Marasco D, Pedone EM, Palumbo R, Leone M
* The Sam-Sam interaction between Ship2 and the EphA2 receptor: design and analysis of peptide inhibitors (45 visite)
Sci Rep (ISSN: 2045-2322electronic, 2045-2322linking), 2017 Dec 12; 7(1): 17474-17474.
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Dato AD, Cunsolo A, Persico M, Santoro AM, D'Urso A, Milardi D, Purrello R, Stefanelli M, Paolesse R, Tundo GR, Sbardella D, Fattorusso C, Coletta M
* Electrostatic Map Of Proteasome alpha-Rings Encodes The Design of Allosteric Porphyrin-Based Inhibitors Able To Affect 20S Conformation By Cooperative Binding (53 visite)
Sci Rep (ISSN: 2045-2322electronic, 2045-2322linking), 2017 Dec 6; 7(1): 17098-17098.
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Oliveri V, Lanza V, Milardi D, Viale M, Maric I, Sgarlata C, Vecchio G
* Amino- and chloro-8-hydroxyquinolines and their copper complexes as proteasome inhibitors and antiproliferative agents (46 visite)
Metallomics (ISSN: 1756-591xelectronic, 1756-5901linking), 2017 Oct 18; 9(10): 1439-1446.
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Tomasello MF, Nardon C, Lanza V, Di Natale G, Pettenuzzo N, Salmaso S, Milardi D, Caliceti P, Pappalardo G, Fregona D
* New comprehensive studies of a gold(III) Dithiocarbamate complex with proven anticancer properties: Aqueous dissolution with cyclodextrins, pharmacokinetics and upstream inhibition of the ubiquitin-proteasome pathway (79 visite)
Eur J Med Chem (ISSN: 1768-3254electronic, 0223-5234linking), 2017 Jun 19; 138: 115-127.
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Palmieri G, Cocca E, Gogliettino M, Valentino R, Ruvo M, Cristofano G, Angiolillo A, Balestrieri M, Rossi M, Di Costanzo A
* Low Erythrocyte Levels of Proteasome and Acyl-Peptide Hydrolase (APEH) Activities in Alzheimer's Disease: A Sign of Defective Proteostasis? (57 visite)
J Alzheimers Dis (ISSN: 1875-8908electronic, 1387-2877linking), 2017; 60(3): 1097-1106.
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Santoro AM, Monaco I, Attanasio F, Lanza V, Pappalardo G, Tomasello MF, Cunsolo A, Rizzarelli E, De Luigi A, Salmona M, Milardi D
* Copper(II) ions affect the gating dynamics of the 20S proteasome: a molecular and in cell study (82 visite)
Sci Rep (ISSN: 2045-2322electronic, 2045-2322linking), 2016 Sep 16; 6: 33444-33444.
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Santoro AM, Cunsolo A, D'Urso A, Sbardella D, Tundo GR, Ciaccio C, Coletta M, Diana D, Fattorusso R, Persico M, Di Dato A, Fattorusso C, Milardi D, Purrello R
* Cationic porphyrins are tunable gatekeepers of the 20S proteasome (462 visite) (PDF 133 visite)
Chemical Science (ISSN: 2041-6539, 2041-6520), 2016; 7(2): 1286-1297.
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Carriero MV, Bifulco K, Minopoli M, Lista L, Maglio O, Mele L, Di Carluccio G, De Rosa M, Pavone V
* UPARANT: a urokinase receptor-derived peptide inhibitor of VEGF-driven angiogenesis with enhanced stability and in vitro and in vivo potency (122 visite)
Mol Cancer Ther Molecular Cancer Therapeutics (ISSN: 1538-8514electronic, 1535-7163linking), 2014 May; 13(5): 1092-1104.
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Ciccarelli M, Rusciano MR, Sorriento D, Basilicata MF, Santulli G, Campiglia P, Bertamino A, De Luca N, Trimarco B, Iaccarino G, Illario M
* CaMKII protects MKP-1 from proteasome degradation in endothelial cells (70 visite)
Cell Signal Cellular Signalling (ISSN: 0898-6568), 2014; 26(10): 2167-2174.
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Bergamo P, Cocca E, Palumbo R, Gogliettino M, Rossi M, Palmieri G
* RedOx status, proteasome and APEH: Insights into anticancer mechanisms of t10, c12-conjugated linoleic acid isomer on A375 melanoma cells (127 visite)
Plos One (ISSN: 1932-6203, 1932-6203electronic), 2013 Nov 19; 8(11): N/D-N/D.
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Galdiero S, Falanga A, Tarallo R, Russo L, Galdiero E, Cantisani M, Morelli G, Galdiero M
* Peptide inhibitors against herpes simplex virus infections (132 visite)
J Pept Sci (ISSN: 1075-2617, 1099-1387, 1075-2617print), 2013 Mar; 19(3): 148-158.
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Santoro AM, Lo Giudice MC, D'Urso A, Lauceri R, Purrello R, Milardi D
* Cationic porphyrins are reversible proteasome inhibitors (143 visite)
J Am Chem Soc (ISSN: 0002-7863, 0002-2786, 1520-5126), 2012 Jun 27; 134(25): 10451-10457.
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Sandomenico A, Russo A, Palmieri G, Bergamo P, Gogliettino M, Falcigno L, Ruvo M
* Small peptide inhibitors of acetyl-peptide hydrolase having an uncommon mechanism of inhibition and a stable bent conformation (99 visite)
J Med Chem (ISSN: 0022-2623, 1520-4804, 0022-2623print), 2012 Mar 8; 55(5): 2102-2111.
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13 Records (12 escludendo Abstract e Conferenze).
Impact factor totale: 66.298 (62.764 escludendo Abstract e Conferenze).
Impact factor a 5 anni totale: 67.228 (63.213 escludendo Abstract e Conferenze).







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