GTP is an allosteric modulator of the interaction between the guanylate-binding protein 1 and the prosurvival kinase PIM1

Giovanni Scambia; M Persico; L Petrella; N Orteca; A Di Dato; M Mariani; M Andreoli; M De Donato; E Novellino; C Ferlini; C. Fattorusso

GTP is an allosteric modulator of the interaction between the guanylate-binding protein 1 and the prosurvival kinase PIM1

Giovanni Scambia, M Persico, L Petrella, N Orteca, A Di Dato, M Mariani, M Andreoli, M De Donato, E Novellino, C Ferlini, C. Fattorusso

Risultato della ricerca: Contributo in rivista › Articolo in rivista

Abstract

GBP1 and PIM1 are known to interact with a molar ratio 1:1. GBP1:PIM1 binding initiates a signaling pathway that induces resistance to common chemotherapeutics such as paclitaxel. Since GBP1 is a large GTPase which undergoes conformational changes in a nucleotide-dependent manner, we investigated the effect of GTP/GDP binding on GBP1:PIM1 interaction by using computational and biological studies. It resulted that only GTP decreases the formation of the GBP1:PIM1 complex through an allosteric mechanism, putting the bases for the identification of new compounds potentially able to revert resistance to paclitaxel.

Lingua originale	English
pagine (da-a)	1-13
Numero di pagine	13
Rivista	European Journal of Medicinal Chemistry
Stato di pubblicazione	Pubblicato - 2014

Keywords

kinase PIM1

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title = "GTP is an allosteric modulator of the interaction between the guanylate-binding protein 1 and the prosurvival kinase PIM1",

abstract = "GBP1 and PIM1 are known to interact with a molar ratio 1:1. GBP1:PIM1 binding initiates a signaling pathway that induces resistance to common chemotherapeutics such as paclitaxel. Since GBP1 is a large GTPase which undergoes conformational changes in a nucleotide-dependent manner, we investigated the effect of GTP/GDP binding on GBP1:PIM1 interaction by using computational and biological studies. It resulted that only GTP decreases the formation of the GBP1:PIM1 complex through an allosteric mechanism, putting the bases for the identification of new compounds potentially able to revert resistance to paclitaxel.",

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author = "Giovanni Scambia and M Persico and L Petrella and N Orteca and {Di Dato}, A and M Mariani and M Andreoli and {De Donato}, M and E Novellino and C Ferlini and C. Fattorusso",

year = "2014",

language = "English",

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journal = "European Journal of Medicinal Chemistry",

issn = "0223-5234",

publisher = "Editions Scientifique & Medical Elsevier:23 Rue Linois, F 75724 Paris Cedex 15 France:011 33 1 71724646, INTERNET: http://www.elsevier.fr, Fax: 011 33 1 71724664",

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TY - JOUR

T1 - GTP is an allosteric modulator of the interaction between the guanylate-binding protein 1 and the prosurvival kinase PIM1

AU - Scambia, Giovanni

AU - Persico, M

AU - Petrella, L

AU - Orteca, N

AU - Di Dato, A

AU - Mariani, M

AU - Andreoli, M

AU - De Donato, M

AU - Novellino, E

AU - Ferlini, C

AU - Fattorusso, C.

PY - 2014

Y1 - 2014

N2 - GBP1 and PIM1 are known to interact with a molar ratio 1:1. GBP1:PIM1 binding initiates a signaling pathway that induces resistance to common chemotherapeutics such as paclitaxel. Since GBP1 is a large GTPase which undergoes conformational changes in a nucleotide-dependent manner, we investigated the effect of GTP/GDP binding on GBP1:PIM1 interaction by using computational and biological studies. It resulted that only GTP decreases the formation of the GBP1:PIM1 complex through an allosteric mechanism, putting the bases for the identification of new compounds potentially able to revert resistance to paclitaxel.

AB - GBP1 and PIM1 are known to interact with a molar ratio 1:1. GBP1:PIM1 binding initiates a signaling pathway that induces resistance to common chemotherapeutics such as paclitaxel. Since GBP1 is a large GTPase which undergoes conformational changes in a nucleotide-dependent manner, we investigated the effect of GTP/GDP binding on GBP1:PIM1 interaction by using computational and biological studies. It resulted that only GTP decreases the formation of the GBP1:PIM1 complex through an allosteric mechanism, putting the bases for the identification of new compounds potentially able to revert resistance to paclitaxel.

KW - kinase PIM1

UR - http://hdl.handle.net/10807/63185

UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-84904711484&partnerid=40&md5=bdf98933eb11761339c7560d28765195

M3 - Article

SP - 1

EP - 13

JO - European Journal of Medicinal Chemistry

JF - European Journal of Medicinal Chemistry

SN - 0223-5234

ER -

GTP is an allosteric modulator of the interaction between the guanylate-binding protein 1 and the prosurvival kinase PIM1

Abstract

Keywords

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