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Application of MIIP pS303 blocking agent to preparation of antitumor drugs

A technology of MIIPS303, anti-tumor drugs, applied in the fields of molecular biology and medicine

Active Publication Date: 2017-09-15
SHANGHAI FIRST PEOPLES HOSPITAL
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0004] In the prior art, there is no report on the development of drugs targeting the phosphorylation site MIIP Ps303 for the treatment of malignant tumors such as abnormal activation of EGFR / PKCε

Method used

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  • Application of MIIP pS303 blocking agent to preparation of antitumor drugs
  • Application of MIIP pS303 blocking agent to preparation of antitumor drugs
  • Application of MIIP pS303 blocking agent to preparation of antitumor drugs

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Experimental program
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Embodiment 1

[0030] 1. EGF induces the interaction between MIIP and RelA

[0031] See Figure 1-Figure 2 , based on the important role of NF-κB signaling pathway and MIIP gene in the process of tumor metastasis, we first investigated whether MIIP gene is involved in the activation of NF-κB signaling pathway induced by epidermal growth factor (EGF). After stable transfection of colon cancer cell HCT116 with Flag-tagged MIIP gene, it was found by co-immunoprecipitation technique that the combination of MIIP and RelA in the nucleus was significantly increased under the stimulation of EGF, but this phenomenon was not found in the cytoplasm . To examine the effect of MIIP on NF-κB activity at the level of translational modification in the nucleus, we knocked down MIIP with shRNA. Interestingly, the reduction of MIIP largely abolished EGF-induced acetylation of lysine 310 in RelA protein , rather than the phosphorylation of serine 536, these two sites are the transcriptional activity-related s...

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Abstract

The invention relates to application of an MIIP pS303 blocking agent to preparation of antitumor drugs. According to researches, PKC epsilon (protein kinase C epsilon) phosphorylated MIIP (migration and invasion inhibitory protein) protein serine 303 (S303) is discovered after EGFR (epidermal growth factor receptor) signal activation, the phosphorylated MIIP can be combined with a significant functional molecule RelA in an NF-kB signal pathway, and accordingly a RelA acetylation level is maintained after EGFR signal activation, RelA mediated migration promoting molecule expression is further promoted, and colonic cancer cell migration is promoted finally. Therefore, drugs can be developed by taking the phosphorylated site (MIIP pS303) as a target and clinically used for treating EGFR / PKC epsilon abnormal activation type malignant tumors. In addition, correlation between colorectal cancer migration and poor prognosis and MIIP S303 phosphorylation is verified, so that reagents for detecting MIIP S303 phosphorylation level can be used for diagnosis or prognosis of colorectal cancers.

Description

technical field [0001] The invention relates to the technical fields of molecular biology and medicine, in particular to the application of MIIP pS303 blocking agent in the preparation of antitumor drugs Background technique [0002] Nuclear factor κb (nuclear factor-Kb, NF-κB) is an important nuclear protein transcription factor belonging to the Rel family, which is ubiquitously present in tissue cells. In the resting state, these proteins are usually present in the cytoplasm in the form of homodimers or heterodimers associated with arrestins. There are two main pathways for the activation of NF-κB, the classical pathway mediated by IκB kinase β (IκB Kinaseβ, IKKβ) and the non-classical pathway dependent on IKKα. Activated NF-κB transfers to the nucleus and plays an important role in regulating the physiological and pathological processes such as cell cycle, apoptosis and metabolism by regulating the expression of a series of pro-inflammatory target genes. A large number ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/00A61P35/00A61P35/04G01N33/574
CPCA61K45/00G01N33/574
Inventor 蒋玉辉周平红陈涛黄文华李静婕
Owner SHANGHAI FIRST PEOPLES HOSPITAL
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