Dataset Information

Kok2020 - IFNalpha-induced signaling in Huh7.5 cells

ABSTRACT: The proposed ODE model describes dynamics of IFNalpha-induced signaling in Huh7.5 cells for a time scale up to 32 hours after stimulation with IFNalpha. The model consists of an IFN receptor model, formation/degradation and cytoplasmic/nuclear shuttling of STAT1-homodimers, STAT1-STAT2-heterodimers and STAT1-STAT2-IRF9 (ISGF3) complexes. On top, formation of feedback proteins STAT1, STAT2, IRF9, USP18, SOCS1, SOCS3 and IRF2 and corresponding influences on IFNalpha signaling dynamics was incorporated. The model was calibrated by dose response and time course measurements over 32 hours as well as time courses for USP18 inhibition and overexpression experiments. As a special focus, the model is able to describe dose-dependent sensitization and desensitization of IFNalpha signaling in form of double treatment experiments at 0h and 24h.

SUBMITTER: Marcus Rosenblatt

PROVIDER: BIOMD0000000959 | BioModels | 2024-09-02

REPOSITORIES: BioModels

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			Action	DRS
	BIOMD0000000959?filename=Kok2020.cps	Other
	BIOMD0000000959?filename=Kok2020.sedml	Other
	BIOMD0000000959?filename=Kok2020.xml	Xml
	BIOMD0000000959?filename=SBML_IFNa_Huh75%20(1).xml	Xml

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Publications

Disentangling molecular mechanisms regulating sensitization of interferon alpha signal transduction.

Kok Frédérique F Rosenblatt Marcus M Teusel Melissa M Nizharadze Tamar T Gonçalves Magalhães Vladimir V Dächert Christopher C Maiwald Tim T Vlasov Artyom A Wäsch Marvin M Tyufekchieva Silvana S Hoffmann Katrin K Damm Georg G Seehofer Daniel D Boettler Tobias T Binder Marco M Timmer Jens J Schilling Marcel M Klingmüller Ursula U

Molecular systems biology 20200701 7

Tightly interlinked feedback regulators control the dynamics of intracellular responses elicited by the activation of signal transduction pathways. Interferon alpha (IFNα) orchestrates antiviral responses in hepatocytes, yet mechanisms that define pathway sensitization in response to prestimulation with different IFNα doses remained unresolved. We establish, based on quantitative measurements obtained for the hepatoma cell line Huh7.5, an ordinary differential equation model for IFNα signal tran ...[more]

PMID: 32696599

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