The Sam Domain of EphA2 receptor and its relevance to cancer: a novel challenge for drug discovery? (334 views)
Curr Med Chem (ISSN: 0929-8673, 1875-533x, 1875-533xelectronic), 2016 Nov 01; 23(42): 4718-4734.
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Paper type: Journal Article, Review,
Impact factor: 3.249, 5-year impact factor: 3.508
Url: Not available.
Keywords: Animals , Drug Discovery Methods , Humans , Peptides Metabolism Pharmacology , Receptor, Epha2 Chemistry Metabolism , Sterile Alpha Motif,
Affiliations:
*** IBB - CNR ***
NATIONAL RESEARCH COUNCIL (CNR) - Institute of Biostructures and Bioimaging, Via Mezzocannone 16 , NAPLES 80134, Italy. marilisa.leone@cnr.it.,
References:
Not available.
Curr Med Chem (ISSN: 0929-8673, 1875-533x, 1875-533xelectronic), 2016 Nov 01; 23(42): 4718-4734.
Export to BibTeX Export to EndNote
Paper type: Journal Article, Review,
Impact factor: 3.249, 5-year impact factor: 3.508
Url: Not available.
Keywords: Animals , Drug Discovery Methods , Humans , Peptides Metabolism Pharmacology , Receptor, Epha2 Chemistry Metabolism , Sterile Alpha Motif,
Affiliations:
*** IBB - CNR ***
NATIONAL RESEARCH COUNCIL (CNR) - Institute of Biostructures and Bioimaging, Via Mezzocannone 16 , NAPLES 80134, Italy. marilisa.leone@cnr.it.,
References:
Not available.
The Sam Domain of EphA2 receptor and its relevance to cancer: a novel challenge for drug discovery?
BACKGROUND: Eph receptors play important functions in developmental processes and diseases and among them EphA2 is well known for its controversial role in cancer. Drug discovery strategies are mainly centered on EphA2 extracellular ligand-binding domain however, the receptor also contains a largely unexplored cytosolic Sam (Sterile alpha motif) domain at the C-terminus. EphA2-Sam binds the Sam domain from the lipid phosphatase Ship2 and the first Sam domain of Odin. Sam-Sam interactions may be important to regulate ligand-induced receptor endocytosis and degradation i.e., processes that could be engaged against tumor malignancy. METHODS: We critically analyzed literature related to a) Eph receptors with particular emphasis on EphA2 and its role in cancer, b) Sam domains, c) heterotypic Sam-Sam interactions involving EphA2-Sam. RESULTS: While literature data indicate that binding of EphA2-Sam to Ship2-Sam should largely generate pro-oncogenic effects in cancer cells, the correlation between EphA2-Sam/Odin-Sam1 complex and the disease is unclear. Recently a few linear peptides encompassing binding interfaces from either Ship2-Sam and Odin-Sam1 have been characterized but failed to efficiently block heterotypic Sam-Sam interactions involving EphA2-Sam due to the lack of a native like fold. CONCLUSION: Molecule antagonists of heterotypic EphA2-Sam associations could work as potential anticancer agents or be implemented as tools to further clarify receptor functions and eventually validate its role as a novel target in the field of anti-cancer drug discovery. Due to the failure of linear peptides there's a crucial need for novel approaches, based on cyclic or helical molecules, to target Sam-Sam interfaces.
BACKGROUND: Eph receptors play important functions in developmental processes and diseases and among them EphA2 is well known for its controversial role in cancer. Drug discovery strategies are mainly centered on EphA2 extracellular ligand-binding domain however, the receptor also contains a largely unexplored cytosolic Sam (Sterile alpha motif) domain at the C-terminus. EphA2-Sam binds the Sam domain from the lipid phosphatase Ship2 and the first Sam domain of Odin. Sam-Sam interactions may be important to regulate ligand-induced receptor endocytosis and degradation i.e., processes that could be engaged against tumor malignancy. METHODS: We critically analyzed literature related to a) Eph receptors with particular emphasis on EphA2 and its role in cancer, b) Sam domains, c) heterotypic Sam-Sam interactions involving EphA2-Sam. RESULTS: While literature data indicate that binding of EphA2-Sam to Ship2-Sam should largely generate pro-oncogenic effects in cancer cells, the correlation between EphA2-Sam/Odin-Sam1 complex and the disease is unclear. Recently a few linear peptides encompassing binding interfaces from either Ship2-Sam and Odin-Sam1 have been characterized but failed to efficiently block heterotypic Sam-Sam interactions involving EphA2-Sam due to the lack of a native like fold. CONCLUSION: Molecule antagonists of heterotypic EphA2-Sam associations could work as potential anticancer agents or be implemented as tools to further clarify receptor functions and eventually validate its role as a novel target in the field of anti-cancer drug discovery. Due to the failure of linear peptides there's a crucial need for novel approaches, based on cyclic or helical molecules, to target Sam-Sam interfaces.
The Sam Domain of EphA2 receptor and its relevance to cancer: a novel challenge for drug discovery?
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The Sam Domain of EphA2 receptor and its relevance to cancer: a novel challenge for drug discovery?
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Vincenzi M, Mercurio FA, Autiero I, Leone M
* Cancer-Related Mutations in the Sam Domains of EphA2 Receptor and Ship2 Lipid Phosphatase: A Computational Study (37 views)
Molecules (ISSN: 1420-3049linking), 2024 Feb 27; 29 (5 ): N/D-N/D.
Impact Factor:
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Vincenzi M, Mercurio FA, Leone M
* Sam Domains in Multiple Diseases (303 views)
Curr Med Chem (ISSN: 0929-8673linking, 1875-533xelectronic), 2020; 27(3): 450-476.
Impact Factor: 3.469
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Mercurio FA, Di Natale C, Pirone L, Marasco D, Calce E, Vincenzi M, Pedone EM, De Luca S, Leone M
* Design and analysis of EphA2-SAM peptide ligands: A multi-disciplinary screening approach (270 views)
Bioorg Chem (ISSN: 0045-2068linking, 1090-2120electronic), 2019 Mar; 84: 434-443.
Impact Factor: 3.929
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Mercurio FA, Pirone L, Di Natale C, Marasco D, Pedone EM, Leone M
* Sam domain-based stapled peptides: Structural analysis and interaction studies with the Sam domains from the EphA2 receptor and the lipid phosphatase Ship2 (421 views)
Bioorg Chem (ISSN: 0045-2068linking, 1090-2120electronic), 2018 Oct; 80: 602-610.
Impact Factor: 3.9
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Zimbone S, Monaco I, Giani F, Pandini G, Copani AG, Giuffrida ML, Rizzarelli E
* Amyloid Beta monomers regulate cyclic adenosine monophosphate response element binding protein functions by activating type-1 insulin-like growth factor receptors in neuronal cells (816 views) (PDF 208 views)
Aging Cell (ISSN: 1474-9726, 1474-9718linking), 2017 Nov 01; 17(1): N/D-N/D.
Impact Factor: 7.627
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Paladino A, Civera M, Belvisi L, Colombo G
High Affinity vs. Native Fibronectin in the Modulation of αvβ3 Integrin Conformational Dynamics: Insights from Computational Analyses and Implications for Molecular Design (172 views)
Plos Comput Biol (ISSN: 1553-734xlinking), 2017 Jan 23; 13 (1 ): e1005334-N/D.
Impact Factor:
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Moroni E, Paladino A, Colombo G
The Dynamics of Drug Discovery (1 views)
Curr Top Med Chem (ISSN: 1568-0266linking), 2015 May 18; 15 (20 ): 2043-2055.
Impact Factor:
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Mercurio FA, Marasco D, Pirone L, Scognamiglio PL, Pedone E, Pellecchia M, Leone M
* Heterotypic Sam-Sam Association Between Odin-Sam1 And Arap3-Sam: Binding Affinity And Structural Insights (506 views)
Chembiochem (ISSN: 1439-4227, 1439-9422, 1439-7633), 2013 Jan 2; 14(1): 100-106.
Impact Factor: 2.92
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Mercurio FA, Marasco D, Pirone L, Pedone E, Pellecchia M, Leone M
* Solution Structure of the First Sam Domain of Odin and Binding Studies with the EphA2 Receptor (582 views)
Biochemistry (ISSN: 0006-2960, 1520-4995, 1520-4995electronic), 2012 Mar 13; 51(10): 2136-2145.
Impact Factor: 3.377
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Calafiore M, Copani A, Deng W
* DNA polymerase-β mediates the neurogenic effect of β-amyloid protein in cultured subventricular zone neurospheres (686 views)
Journal Of Neuroscience Research (ISSN: 0360-4012), 2012 Mar; 90(3): 559-567.
Impact Factor: 2.974
View Export to BibTeX Export to EndNote
* Cancer-Related Mutations in the Sam Domains of EphA2 Receptor and Ship2 Lipid Phosphatase: A Computational Study (37 views)
Molecules (ISSN: 1420-3049linking), 2024 Feb 27; 29 (5 ): N/D-N/D.
Impact Factor:
View Export to BibTeX Export to EndNote
Vincenzi M, Mercurio FA, Leone M
* Sam Domains in Multiple Diseases (303 views)
Curr Med Chem (ISSN: 0929-8673linking, 1875-533xelectronic), 2020; 27(3): 450-476.
Impact Factor: 3.469
View Export to BibTeX Export to EndNote
Mercurio FA, Di Natale C, Pirone L, Marasco D, Calce E, Vincenzi M, Pedone EM, De Luca S, Leone M
* Design and analysis of EphA2-SAM peptide ligands: A multi-disciplinary screening approach (270 views)
Bioorg Chem (ISSN: 0045-2068linking, 1090-2120electronic), 2019 Mar; 84: 434-443.
Impact Factor: 3.929
View Export to BibTeX Export to EndNote
Mercurio FA, Pirone L, Di Natale C, Marasco D, Pedone EM, Leone M
* Sam domain-based stapled peptides: Structural analysis and interaction studies with the Sam domains from the EphA2 receptor and the lipid phosphatase Ship2 (421 views)
Bioorg Chem (ISSN: 0045-2068linking, 1090-2120electronic), 2018 Oct; 80: 602-610.
Impact Factor: 3.9
View Export to BibTeX Export to EndNote
Zimbone S, Monaco I, Giani F, Pandini G, Copani AG, Giuffrida ML, Rizzarelli E
* Amyloid Beta monomers regulate cyclic adenosine monophosphate response element binding protein functions by activating type-1 insulin-like growth factor receptors in neuronal cells (816 views) (PDF 208 views)
Aging Cell (ISSN: 1474-9726, 1474-9718linking), 2017 Nov 01; 17(1): N/D-N/D.
Impact Factor: 7.627
View Export to BibTeX Export to EndNote
Paladino A, Civera M, Belvisi L, Colombo G
High Affinity vs. Native Fibronectin in the Modulation of αvβ3 Integrin Conformational Dynamics: Insights from Computational Analyses and Implications for Molecular Design (172 views)
Plos Comput Biol (ISSN: 1553-734xlinking), 2017 Jan 23; 13 (1 ): e1005334-N/D.
Impact Factor:
View Export to BibTeX Export to EndNote
Moroni E, Paladino A, Colombo G
The Dynamics of Drug Discovery (1 views)
Curr Top Med Chem (ISSN: 1568-0266linking), 2015 May 18; 15 (20 ): 2043-2055.
Impact Factor:
View Export to BibTeX Export to EndNote
Mercurio FA, Marasco D, Pirone L, Scognamiglio PL, Pedone E, Pellecchia M, Leone M
* Heterotypic Sam-Sam Association Between Odin-Sam1 And Arap3-Sam: Binding Affinity And Structural Insights (506 views)
Chembiochem (ISSN: 1439-4227, 1439-9422, 1439-7633), 2013 Jan 2; 14(1): 100-106.
Impact Factor: 2.92
View Export to BibTeX Export to EndNote
Mercurio FA, Marasco D, Pirone L, Pedone E, Pellecchia M, Leone M
* Solution Structure of the First Sam Domain of Odin and Binding Studies with the EphA2 Receptor (582 views)
Biochemistry (ISSN: 0006-2960, 1520-4995, 1520-4995electronic), 2012 Mar 13; 51(10): 2136-2145.
Impact Factor: 3.377
View Export to BibTeX Export to EndNote
Calafiore M, Copani A, Deng W
* DNA polymerase-β mediates the neurogenic effect of β-amyloid protein in cultured subventricular zone neurospheres (686 views)
Journal Of Neuroscience Research (ISSN: 0360-4012), 2012 Mar; 90(3): 559-567.
Impact Factor: 2.974
View Export to BibTeX Export to EndNote
10 Records (10 excluding Abstracts).
Total impact factor: 28.196 (28.196 excluding Abstracts).
Total 5 year impact factor: 28.634 (28.634 excluding Abstracts).
Total impact factor: 28.196 (28.196 excluding Abstracts).
Total 5 year impact factor: 28.634 (28.634 excluding Abstracts).
334 views. Last view on Sunday 08 September 2024, 14:03:45
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