RIP1-HAT1-SIRT Complex Identification and Targeting in Treatment and Prevention of Cancer (308 views)
Clin Cancer Res (ISSN: 1078-0432print, 1078-0432linking), 2018 Jun 15; 24(12): 2886-2900.
Export to BibTeX Export to EndNote
Paper type: Journal Article,
Impact factor: 6.488, 5-year impact factor: 6.646
Url: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85052287980&doi=10.1158%2f1078-0432.CCR-17-3081&partnerID=40&md5=40eb37bac795274af9b9ca4d6a11c13c
Keywords: 12 Dimethylbenz[a]anthracene, Caspase 8, Histone Acetyltransferase, Hydrolase Inhibitor, Mc 2494, Phosphotransferase, Rip1 Kinase, Rip3 Kinase, Sirtuin 1, Unclassified Drug, Animal Experiment, Animal Model, Apoptosis, Article, Breast Cancer, Cancer Model, Cancer Prevention, Cancer Therapy, Cell Death, Complex Formation, Controlled Study, Enzymatic Assay, Ex Vivo Study, Female, Flow Cytometry, Genetic Transfection, Human, Human Cell, Immunoprecipitation, In Vitro Study, In Vivo Study, Infant, Malignant Neoplasm, Mass Spectrometry, Mouse, Mouse Model, Mutagenesis, Nonhuman, Priority Journal, Protein Acetylation, Protein Protein Interaction, Transcriptomics, Tumor Xenograft,
Affiliations:
*** IBB - CNR ***
Dipartimento di Medicina di Precisione, Universita degli Studi della Campania "Luigi Vanvitelli", Napoli, Italy., Dipartimento di Chimica e Tecnologie del Farmaco, "Sapienza" Universita di Roma, Roma, Italy., Dipartimento di Scienze e Tecnologie Ambientali Biologiche e Farmaceutiche, Universita della Campania Luigi Vanvitelli, Caserta, Italy., Biopulse s.r.l., Napoli, Italy., SAFU Department, Regina Elena Cancer Institute, Rome, Italy., Istituto di Biostrutture e Bioimmagini, CNR, and CIRPeB, Napoli, Italy., Center of Excellence on Neurodegenerative Diseases and Department of Pharmacological Sciences, Universita di Milano, Milano, Italy., Department of Molecular Biology, Radboud University, Nijmegen, the Netherlands., Mouse and Animal Pathology Lab, Fondazione Filarete, Milano, Italy., Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania., CEINGE, Naples, Italy., Dipartimento di Biochimica e Biotecnologie Mediche, Universita Federico II, Napoli, Italy., Pasteur-Fondazione Cenci Bolognetti, Sapienza Universita di Roma, Roma, Italy., Dipartimento di Medicina di Precisione, Universita degli Studi della Campania "Luigi Vanvitelli", Napoli, Italy. lucia.altucci@unicampania.it.,
References:
Not available.
Clin Cancer Res (ISSN: 1078-0432print, 1078-0432linking), 2018 Jun 15; 24(12): 2886-2900.
Export to BibTeX Export to EndNote
Paper type: Journal Article,
Impact factor: 6.488, 5-year impact factor: 6.646
Url: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85052287980&doi=10.1158%2f1078-0432.CCR-17-3081&partnerID=40&md5=40eb37bac795274af9b9ca4d6a11c13c
Keywords: 12 Dimethylbenz[a]anthracene, Caspase 8, Histone Acetyltransferase, Hydrolase Inhibitor, Mc 2494, Phosphotransferase, Rip1 Kinase, Rip3 Kinase, Sirtuin 1, Unclassified Drug, Animal Experiment, Animal Model, Apoptosis, Article, Breast Cancer, Cancer Model, Cancer Prevention, Cancer Therapy, Cell Death, Complex Formation, Controlled Study, Enzymatic Assay, Ex Vivo Study, Female, Flow Cytometry, Genetic Transfection, Human, Human Cell, Immunoprecipitation, In Vitro Study, In Vivo Study, Infant, Malignant Neoplasm, Mass Spectrometry, Mouse, Mouse Model, Mutagenesis, Nonhuman, Priority Journal, Protein Acetylation, Protein Protein Interaction, Transcriptomics, Tumor Xenograft,
Affiliations:
*** IBB - CNR ***
Dipartimento di Medicina di Precisione, Universita degli Studi della Campania "Luigi Vanvitelli", Napoli, Italy., Dipartimento di Chimica e Tecnologie del Farmaco, "Sapienza" Universita di Roma, Roma, Italy., Dipartimento di Scienze e Tecnologie Ambientali Biologiche e Farmaceutiche, Universita della Campania Luigi Vanvitelli, Caserta, Italy., Biopulse s.r.l., Napoli, Italy., SAFU Department, Regina Elena Cancer Institute, Rome, Italy., Istituto di Biostrutture e Bioimmagini, CNR, and CIRPeB, Napoli, Italy., Center of Excellence on Neurodegenerative Diseases and Department of Pharmacological Sciences, Universita di Milano, Milano, Italy., Department of Molecular Biology, Radboud University, Nijmegen, the Netherlands., Mouse and Animal Pathology Lab, Fondazione Filarete, Milano, Italy., Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania., CEINGE, Naples, Italy., Dipartimento di Biochimica e Biotecnologie Mediche, Universita Federico II, Napoli, Italy., Pasteur-Fondazione Cenci Bolognetti, Sapienza Universita di Roma, Roma, Italy., Dipartimento di Medicina di Precisione, Universita degli Studi della Campania "Luigi Vanvitelli", Napoli, Italy. lucia.altucci@unicampania.it.,
References:
Not available.
RIP1-HAT1-SIRT Complex Identification and Targeting in Treatment and Prevention of Cancer
Purpose: Alteration in cell death is a hallmark of cancer. A functional role regulating survival, apoptosis, and necroptosis has been attributed to RIP1/3 complexes. Experimental Design: We have investigated the role of RIP1 and the effects of MC2494 in cell death induction, using different methods as flow cytometry, transcriptome analysis, immunoprecipitation, enzymatic assays, transfections, mutagenesis, and in vivo studies with different mice models. Results: Here, we show that RIP1 is highly expressed in cancer, and we define a novel RIP1/3–SIRT1/2–HAT1/4 complex. Mass spectrometry identified five acetylations in the kinase and death domain of RIP1. The novel characterized pan-SIRT inhibitor, MC2494, increases RIP1 acetylation at two additional sites in the death domain. Mutagenesis of the acetylated lysine decreases RIP1-dependent cell death, suggesting a role for acetylation of the RIP1 complex in cell death modulation. Accordingly, MC2494 displays tumor-selective potential in vitro, in leukemic blasts ex vivo, and in vivo in both xenograft and allograft cancer models. Mechanistically, MC2494 induces bona fide tumor-restricted acetylated RIP1/caspase-8–mediated apoptosis. Excitingly, MC2494 displays tumor-preventive activity by blocking 7,12-dimethylbenz(α)anthracene–induced mammary gland hyperproliferation in vivo. Conclusions: These preventive features might prove useful in patients who may benefit from a recurrence-preventive approach with low toxicity during follow-up phases and in cases of established cancer predisposition. Thus, targeting the newly identified RIP1 complex may represent an attractive novel paradigm in cancer treatment and prevention. ©2018 American Association for Cancer Research.
Purpose: Alteration in cell death is a hallmark of cancer. A functional role regulating survival, apoptosis, and necroptosis has been attributed to RIP1/3 complexes. Experimental Design: We have investigated the role of RIP1 and the effects of MC2494 in cell death induction, using different methods as flow cytometry, transcriptome analysis, immunoprecipitation, enzymatic assays, transfections, mutagenesis, and in vivo studies with different mice models. Results: Here, we show that RIP1 is highly expressed in cancer, and we define a novel RIP1/3–SIRT1/2–HAT1/4 complex. Mass spectrometry identified five acetylations in the kinase and death domain of RIP1. The novel characterized pan-SIRT inhibitor, MC2494, increases RIP1 acetylation at two additional sites in the death domain. Mutagenesis of the acetylated lysine decreases RIP1-dependent cell death, suggesting a role for acetylation of the RIP1 complex in cell death modulation. Accordingly, MC2494 displays tumor-selective potential in vitro, in leukemic blasts ex vivo, and in vivo in both xenograft and allograft cancer models. Mechanistically, MC2494 induces bona fide tumor-restricted acetylated RIP1/caspase-8–mediated apoptosis. Excitingly, MC2494 displays tumor-preventive activity by blocking 7,12-dimethylbenz(α)anthracene–induced mammary gland hyperproliferation in vivo. Conclusions: These preventive features might prove useful in patients who may benefit from a recurrence-preventive approach with low toxicity during follow-up phases and in cases of established cancer predisposition. Thus, targeting the newly identified RIP1 complex may represent an attractive novel paradigm in cancer treatment and prevention. ©2018 American Association for Cancer Research.
RIP1-HAT1-SIRT Complex Identification and Targeting in Treatment and Prevention of Cancer
No results. |
RIP1-HAT1-SIRT Complex Identification and Targeting in Treatment and Prevention of Cancer
Other filter: ([btitle,keywords] "12 Dimethylbenz[a]an ...
Deplano A, Morgillo CM, Demurtas M, Bjorklund E, Cipriano M, Svensson M, Hashemian S, Smaldone G, Pedone E, Luque FJ, Cabiddu MG, Novellino E, Fowler CJ, Catalanotti B, Onnis V
* Novel propanamides as fatty acid amide hydrolase inhibitors (438 views)
Eur J Med Chem (ISSN: 0223-5234, 1768-3254, 0223-5234linking), 2017 Aug 18; 136: 523-542.
Impact Factor: 4.816
View Export to BibTeX Export to EndNote
Milardi D, Pappalardo M
* Molecular dynamics: New advances in drug discovery (511 views)
Eur J Med Chem (ISSN: 0223-5234, 1768-3254, 0223-5234linking), 2015; 91: 1-3.
Impact Factor: 3.902
View Export to BibTeX Export to EndNote
Dynkevich Y, Rother KI, Whitford I, Qureshi S, Galiveeti S, Szulc AL, Danoff A, Breen TL, Kaviani N, Shanik MH, LeRoith D, Vigneri R, Koch CA, Roth J
* Tumors, IGF-2, and Hypoglycemia: Insights From the Clinic, the Laboratory, and the Historical Archive (2349 views)
Endocrine Reviews (ISSN: 0163-769x), 2013 Dec; 34(6): 798-826.
Impact Factor: 19.358
View Export to BibTeX Export to EndNote
Rosa R, Marciano R, Malapelle U, Formisano L, Nappi L, D'Amato C, D'Amato V, Damiano V, Marf G, Del Vecchio S, Zannetti A, Greco A, De Stefano A, Carlomagno C, Veneziani BM, Troncone G, De Placido S, Bianco R
* Sphingosine Kinase 1 Overexpression Contributes to Cetuximab Resistance in Human Colorectal Cancer Models (779 views)
Clin Cancer Res (ISSN: 1078-0432, 1078-0432linking, 1078-0432print), 2013 Jan 1; 19(1): 138-147.
Impact Factor: 8.193
View Export to BibTeX Export to EndNote
Milite C, Castellano S, Benedetti R, Tosco A, Ciliberti C, Vicidomini C, Boully L, Franci G, Altucci L, Mai A, Sbardella G
* Modulation of the activity of histone acetyltransferases by long chain alkylidenemalonates (LoCAMs) (454 views)
Bioorg Med Chem (ISSN: 0968-0896, 1464-3391, 1464-3391electronic), 2011 Jun 15; 19(12): 3690-3701.
Impact Factor: 2.921
View Export to BibTeX Export to EndNote
Marasco D, Perretta G, Sabatella M, Ruvo M
* Past and Future Perspectives of Synthetic Peptide Libraries (683 views)
Curr Protein Pept Sci (ISSN: 1389-2037, 1389-2037linking), 2008 Oct; 9(5): 447-467.
Impact Factor: 3.011
View Export to BibTeX Export to EndNote
Sbardella G, Castellano S, Vicidomini C, Rotili D, Nebbioso A, Miceli M, Altucci L, Mai A
* Identification of long chain alkylidenemalonates as novel small molecule modulators of histone acetyltransferases (418 views)
Bioorganic & Medicinal Chemistry Letters (ISSN: 0960-894x), 2008 May 1; 18(9): 2788-2792.
Impact Factor: 2.531
View Export to BibTeX Export to EndNote
Mai A, Rotili D, Tarantino D, Ornaghi P, Tosi F, Vicidomini C, Sbardella G, Nebbioso A, Miceli M, Altucci L, Filetici P
* Small-molecule inhibitors of histone acetyltransferase activity: Identification and biological properties (842 views)
J Med Chem (ISSN: 0022-2623, 1520-4804, 0022-2623print), 2006 Nov 16; 49(23): 6897-6907.
Impact Factor: 5.115
View Export to BibTeX Export to EndNote
Mai A, Rotili D, Ornaghi P, Tosi F, Vicidomini C, Sardella G, Nebbioso A, Altucci L, Filatici P
* Identification of small molecules inhibitors of GCN5 histone acetyltransferase activity (321 views)
Arkivoc (ISSN: 1424-6376), 2006; 6(VIII): 24-37.
Impact Factor: 0.8
View Export to BibTeX Export to EndNote
* Novel propanamides as fatty acid amide hydrolase inhibitors (438 views)
Eur J Med Chem (ISSN: 0223-5234, 1768-3254, 0223-5234linking), 2017 Aug 18; 136: 523-542.
Impact Factor: 4.816
View Export to BibTeX Export to EndNote
Milardi D, Pappalardo M
* Molecular dynamics: New advances in drug discovery (511 views)
Eur J Med Chem (ISSN: 0223-5234, 1768-3254, 0223-5234linking), 2015; 91: 1-3.
Impact Factor: 3.902
View Export to BibTeX Export to EndNote
Dynkevich Y, Rother KI, Whitford I, Qureshi S, Galiveeti S, Szulc AL, Danoff A, Breen TL, Kaviani N, Shanik MH, LeRoith D, Vigneri R, Koch CA, Roth J
* Tumors, IGF-2, and Hypoglycemia: Insights From the Clinic, the Laboratory, and the Historical Archive (2349 views)
Endocrine Reviews (ISSN: 0163-769x), 2013 Dec; 34(6): 798-826.
Impact Factor: 19.358
View Export to BibTeX Export to EndNote
Rosa R, Marciano R, Malapelle U, Formisano L, Nappi L, D'Amato C, D'Amato V, Damiano V, Marf G, Del Vecchio S, Zannetti A, Greco A, De Stefano A, Carlomagno C, Veneziani BM, Troncone G, De Placido S, Bianco R
* Sphingosine Kinase 1 Overexpression Contributes to Cetuximab Resistance in Human Colorectal Cancer Models (779 views)
Clin Cancer Res (ISSN: 1078-0432, 1078-0432linking, 1078-0432print), 2013 Jan 1; 19(1): 138-147.
Impact Factor: 8.193
View Export to BibTeX Export to EndNote
Milite C, Castellano S, Benedetti R, Tosco A, Ciliberti C, Vicidomini C, Boully L, Franci G, Altucci L, Mai A, Sbardella G
* Modulation of the activity of histone acetyltransferases by long chain alkylidenemalonates (LoCAMs) (454 views)
Bioorg Med Chem (ISSN: 0968-0896, 1464-3391, 1464-3391electronic), 2011 Jun 15; 19(12): 3690-3701.
Impact Factor: 2.921
View Export to BibTeX Export to EndNote
Marasco D, Perretta G, Sabatella M, Ruvo M
* Past and Future Perspectives of Synthetic Peptide Libraries (683 views)
Curr Protein Pept Sci (ISSN: 1389-2037, 1389-2037linking), 2008 Oct; 9(5): 447-467.
Impact Factor: 3.011
View Export to BibTeX Export to EndNote
Sbardella G, Castellano S, Vicidomini C, Rotili D, Nebbioso A, Miceli M, Altucci L, Mai A
* Identification of long chain alkylidenemalonates as novel small molecule modulators of histone acetyltransferases (418 views)
Bioorganic & Medicinal Chemistry Letters (ISSN: 0960-894x), 2008 May 1; 18(9): 2788-2792.
Impact Factor: 2.531
View Export to BibTeX Export to EndNote
Mai A, Rotili D, Tarantino D, Ornaghi P, Tosi F, Vicidomini C, Sbardella G, Nebbioso A, Miceli M, Altucci L, Filetici P
* Small-molecule inhibitors of histone acetyltransferase activity: Identification and biological properties (842 views)
J Med Chem (ISSN: 0022-2623, 1520-4804, 0022-2623print), 2006 Nov 16; 49(23): 6897-6907.
Impact Factor: 5.115
View Export to BibTeX Export to EndNote
Mai A, Rotili D, Ornaghi P, Tosi F, Vicidomini C, Sardella G, Nebbioso A, Altucci L, Filatici P
* Identification of small molecules inhibitors of GCN5 histone acetyltransferase activity (321 views)
Arkivoc (ISSN: 1424-6376), 2006; 6(VIII): 24-37.
Impact Factor: 0.8
View Export to BibTeX Export to EndNote
9 Records (9 excluding Abstracts).
Total impact factor: 50.647 (50.647 excluding Abstracts).
Total 5 year impact factor: 56.584 (56.584 excluding Abstracts).
Total impact factor: 50.647 (50.647 excluding Abstracts).
Total 5 year impact factor: 56.584 (56.584 excluding Abstracts).
308 views. Last view on Tuesday 24 September 2024, 14:56:57
ibb.cnr.it
