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12541_6517002_computers_in_biology_and_medicine_jurado_et_al-2021.pdf (1.74 MB)
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Data de publicació

2021-04-20

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cc by (c) Jurado, Manuel et al., 2021
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/178662

Stochastic modulation evidences a transitory EGF-Ras-ERK MAPK activity induced by PRMT5

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Recurs relacionat

https://doi.org/10.1016/j.compbiomed.2021.104339

Resum

The extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase (MAPK) pathway involves a three-step cascade of kinases that transduce signals and promote processes such as cell growth, development, and apoptosis. An aberrant response of this pathway is related to the proliferation of cell diseases and tumors. By using simulation modeling, we document that the protein arginine methyltransferase 5 (PRMT5) modulates the MAPK pathway and thus avoids an aberrant behavior. PRMT5 methylates the Raf kinase, reducing its catalytic activity and thereby, reducing the activation of ERK in time and amplitude. Two minimal computational models of the epidermal growth factor (EGF)-Ras-ERK MAPK pathway influenced by PRMT5 were proposed: a first model in which PRMT5 is activated by EGF and a second one in which PRMT5 is stimulated by the cascade response. The reported results show that PRMT5 reduces the time duration and the expression of the activated ERK in both cases, but only in the first model PRMT5 limits the EGF range that generates an ERK activation. Based on our data, we propose the protein PRMT5 as a regulatory factor to develop strategies to fight against an excessive activity of the MAPK pathway, which could be of use in chronic diseases and cancer.

Matèries

Proteïnes quinases, Apoptosi, Càncer

Matèries (anglès)

Protein kinases, Apoptosis, Cancer

Citació

Col·leccions

Articles publicats en revistes (Enginyeria Electrònica i Biomèdica)
Articles publicats en revistes (Bioquímica i Biomedicina Molecular)
Articles publicats en revistes (Institut de Bioenginyeria de Catalunya (IBEC))
Articles publicats en revistes (Institut de Nanociència i Nanotecnologia (IN2UB))
Articles publicats en revistes (Institut de Recerca Biomèdica (IRB Barcelona))

Citació

JURADO, Manuel, CASTAÑO LINARES, Óscar, ZORZANO OLARTE, Antonio. Stochastic modulation evidences a transitory EGF-Ras-ERK MAPK activity induced by PRMT5. _Computers in Biology and Medicine_. 2021. Vol. 133, núm. 104339. [consulta: 25 de febrer de 2026]. [Disponible a: https://hdl.handle.net/2445/178662]

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