Cell Death Differ: TRIM22 activates the NF-B signal by accelerating I-B alpha degradation.

The NF-B signal transducting path is initially found to be characterized by the immune system and has been found to be associated with many characteristics of cancer development, including cell proliferation, angiogenesy, and resistance to treatment.
consistent with other malignant tumors, high compositional activity of NF-B has also been observed in human glioblastoma (GBM) and can promote interstitiotic differentiation and therapeutic resistance to the disease.
the molecular mechanisms involved have yet to be studied.
trim protein family, a sub-family of RENING-type E3 ubiquitin connective enzymes, can act as a key regulatory factor in the development of a variety of cancers, including GBM, by regulating the transcriptional activity of NF-B.
In this study, researchers explored the role of TRIM proteins in the development of GBM, and by using NF-B-driven luciferase to report genetic systems and screening in public databases, the researchers identified TRIM22 as a potential activator of NF-B signals in GBM cells.
in-body experiments and in-place transplant tumor model studies have shown that knocking out TRIM22 by Cas9-sgRNA technology leads to a decrease in GBM cell proliferation, while over-expression trim22 enhances cell proliferation capacity.
the researchers found that two mutants of the TRIM22 protein: one is missing the protein-critical REING-finger domain, and the other is the amino acid changes at two active bits of THEN E3 connective enzyme (C15/18A), which do not promote the GBM cell proliferation process, indicating that TRIM22's E3 connective enzyme activity has the characteristics of promoting cell proliferation.
immunoprecipitation experiments showed that TRIM22 was able to accelerate its degradation by combining the Ubidian pathway of the NF-B negative regulatory factor I-B alpha to induce the K48 connection.
TRIM22 is also able to form a complex with the NF-B upstream regulator IKK gamma, promoting the Ubibinization pathway of the K63 connection and inducing phosphate of IKK alpha/beta and I-B alpha.
the expression of the non-phosphorylated mutant srI-B alpha in the GBM cell line inhibits the proliferative effect of TRIM22.
, tissue chip analysis results from GBM samples showed that TRIM22's expression level increased, and TRIM22's high expression level was associated with clinical parameters of aggressive glioma.
in summary, the results show that in human glioblastoma, TRIM22 is able to activate the NF-B signal by translating and modifying two key regulators in the NF-B signaling path.
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