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Method for inducing programmed cell necrosis artificially

A technology of programmed necrosis and cell generation, applied in biochemical equipment and methods, genetic engineering, botanical equipment and methods, etc., can solve problems such as unclear heterologous polymer signal transmission

Inactive Publication Date: 2015-06-24
XIAMEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, it was unclear how the fibrous heteropolymers signaled

Method used

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  • Method for inducing programmed cell necrosis artificially
  • Method for inducing programmed cell necrosis artificially
  • Method for inducing programmed cell necrosis artificially

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Embodiment 1

[0025] 1) Design and optimize the aggregation system.

[0026] Since the dimerization / multimerization linker used in the present invention is a protein endogenously expressed in cells, in order to avoid endogenous interference, the present invention has been optimized and modified according to the following documents:

[0027] Littlewood TD, Hancock DC, Danielian PS, Parker MG, Evan GI. A modified oestrogen receptor ligand-binding domain as an improved switch for the regulation of heterologous proteins. Nucleic Acids Res 1995, 23(10):1686-1690.

[0028] Pollock R, Giel M, Linher K, Clackson T. Regulation of endogenous gene expression with a small-molecule dimerizer. Nat Biotechnol 2002, 20(7): 729-733.

[0029] Clackson T, Yang W, Rozamus LW, Hatada M, Amara JF, Rollins CT, et al. Redesigning an FKBP-ligand interface to generate chemical dimerizers with novel specificity. Proc Natl Acad Sci U S A 1998, 95(18): 10437-10442 .

[0030] It includes four parts:

[0031] a. For H...

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Abstract

The invention discloses a method for inducing programmed cell necrosis by RIP3 molecule dimerization / multimerization. The RIP3 is a switch protein for mediating cell to have programmed necrosis. According to the method disclosed by the invention, RIP3 fusion protein with a polymerization joint is manually constructed, and a cell for expressing the fusion protein can generate necrosis death under stimulation of a polymerization inductor. The method disclosed by the invention is expected to be used for screening an inhibitor for programmed necrosis.

Description

technical field [0001] The invention belongs to the field of biotechnology, and in particular relates to a method for artificially inducing programmed necrosis of cells. Background technique [0002] Programmed necrosis is a way of programmed cell death 1 . Cells undergoing programmed necrosis, morphologically, mainly manifested as cell swelling and cell membrane rupture 1 . Programmed necrosis is a mechanism by which the host defends against pathogens, but over-activated programmed necrosis can also lead to pathological processes such as tissue inflammation 1 . [0003] Programmed necrosis can be induced by many different extracellular stimuli, including tumor necrosis factor (TNF). TNF binds tumor necrosis factor receptor 1 (TNFR1) on the cell membrane surface, triggers the trimerization of the receptor molecule and induces the intramembrane protein domain of the receptor molecule to recruit the linker receptor-interacting protein kinase 1 (RIP1), TNFR1-related death ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12N15/867C12N15/62
Inventor 韩家淮吴晓男黄哲李渊越汪雪坤杨章华
Owner XIAMEN UNIV
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