Transition and identification of pathological states in p53 dynamics for therapeutic intervention

Abstract We study a minimal model of the stress-driven p53 regulatory network that includes competition between active and mutant forms of the tumor-suppressor gene p53. Depending on the nature and level of the external stress signal, four distinct dynamical states of p53 are observed. These states...

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Autores principales:	Amit Jangid, Md. Zubbair Malik, Ram Ramaswamy, R. K. Brojen Singh
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8b1c7848d1d04c9482ce50d506332f2f
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spelling	oai:doaj.org-article:8b1c7848d1d04c9482ce50d506332f2f2021-12-02T13:57:49ZTransition and identification of pathological states in p53 dynamics for therapeutic intervention10.1038/s41598-021-82054-12045-2322https://doaj.org/article/8b1c7848d1d04c9482ce50d506332f2f2021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-82054-1https://doaj.org/toc/2045-2322Abstract We study a minimal model of the stress-driven p53 regulatory network that includes competition between active and mutant forms of the tumor-suppressor gene p53. Depending on the nature and level of the external stress signal, four distinct dynamical states of p53 are observed. These states can be distinguished by different dynamical properties which associate to active, apoptotic, pre-malignant and cancer states. Transitions between any two states, active, apoptotic, and cancer, are found to be unidirectional and irreversible if the stress signal is either oscillatory or constant. When the signal decays exponentially, the apoptotic state vanishes, and for low stress the pre-malignant state is bounded by two critical points, allowing the system to transition reversibly from the active to the pre-malignant state. For significantly large stress, the range of the pre-malignant state expands, and the system moves to irreversible cancerous state, which is a stable attractor. This suggests that identification of the pre-malignant state may be important both for therapeutic intervention as well as for drug delivery.Amit JangidMd. Zubbair MalikRam RamaswamyR. K. Brojen SinghNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Amit Jangid Md. Zubbair Malik Ram Ramaswamy R. K. Brojen Singh Transition and identification of pathological states in p53 dynamics for therapeutic intervention
description	Abstract We study a minimal model of the stress-driven p53 regulatory network that includes competition between active and mutant forms of the tumor-suppressor gene p53. Depending on the nature and level of the external stress signal, four distinct dynamical states of p53 are observed. These states can be distinguished by different dynamical properties which associate to active, apoptotic, pre-malignant and cancer states. Transitions between any two states, active, apoptotic, and cancer, are found to be unidirectional and irreversible if the stress signal is either oscillatory or constant. When the signal decays exponentially, the apoptotic state vanishes, and for low stress the pre-malignant state is bounded by two critical points, allowing the system to transition reversibly from the active to the pre-malignant state. For significantly large stress, the range of the pre-malignant state expands, and the system moves to irreversible cancerous state, which is a stable attractor. This suggests that identification of the pre-malignant state may be important both for therapeutic intervention as well as for drug delivery.
format	article
author	Amit Jangid Md. Zubbair Malik Ram Ramaswamy R. K. Brojen Singh
author_facet	Amit Jangid Md. Zubbair Malik Ram Ramaswamy R. K. Brojen Singh
author_sort	Amit Jangid
title	Transition and identification of pathological states in p53 dynamics for therapeutic intervention
title_short	Transition and identification of pathological states in p53 dynamics for therapeutic intervention
title_full	Transition and identification of pathological states in p53 dynamics for therapeutic intervention
title_fullStr	Transition and identification of pathological states in p53 dynamics for therapeutic intervention
title_full_unstemmed	Transition and identification of pathological states in p53 dynamics for therapeutic intervention
title_sort	transition and identification of pathological states in p53 dynamics for therapeutic intervention
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/8b1c7848d1d04c9482ce50d506332f2f
work_keys_str_mv	AT amitjangid transitionandidentificationofpathologicalstatesinp53dynamicsfortherapeuticintervention AT mdzubbairmalik transitionandidentificationofpathologicalstatesinp53dynamicsfortherapeuticintervention AT ramramaswamy transitionandidentificationofpathologicalstatesinp53dynamicsfortherapeuticintervention AT rkbrojensingh transitionandidentificationofpathologicalstatesinp53dynamicsfortherapeuticintervention
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Transition and identification of pathological states in p53 dynamics for therapeutic intervention

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