Nat Commun Customer Story: Mimic modification regulates glutamine absorption and metabolism in tumor cells

Metabolism is the basis of energy and material sources for cells and body life activities, and its steady-state equilibrium is an important guarantee for the body to cope with changes in internal and external space-time [1, 2].

Neddylation is a post-translational modification of a protein that regulates protein activity or function without mediating its degradation by the 26S proteasome[5

On May 31, 2022, the team of Professor Sun Yi of the Second Affiliated Hospital of Zhejiang University School of Medicine/Institute of Translational Medicine of Zhejiang University published a speech entitled Nutdylation inhibition induces glutamine uptake and metabolism by targeting CRL3SPOP E3 ligase in cancer at Nature Communications Cells' research paper, which reports that mimic modifications regulate glutamine uptake and metabolism

Previous work by the researchers found that inhibiting mitotropylation modification using the small molecule MLN4924, a small molecule inhibitor of the deacetylating activating enzyme, can induce the kinetic transition of mitochondria from division to fusion, disrupt mitochondrial function, and promote glycolysis by activating PKM2 [9

In order to clarify the mechanism of ASCT2 accumulation after the inhibition of mimicration modification, combined with bioinformatics and biochemical experiments, the researchers found that the ASCT2 protein contained the classical binding motif of the linker protein POP in the CRL3 E3 ubiquitin ligase, and SPOP promoted the polyubiquitination degradation of the K48-linked ASCT2 protein and reduced its stability

In view of the protective effect of cellular glutamine absorption and metabolism caused by inhibition of mitrification on tumor cell survival, in order to further reveal the effect of targeted mitrification pathway and cellular glutamine metabolism on tumor cell growth, the researchers used MLN492 combined with ASCT2 inhibitor V-9302, and the results of in vitro cell experiments and in vivo tumor model experiments showed that the targeting mimicization pathway and glutamine absorption could significantly inhibit tumor cell proliferation

Illustration: Study mode diagram

Dr.

References

1.

2.

3.

4.

5.

6.

7.
Vogl, A.
M.
, et al.
, Global site-specific neddylation profiling reveals that NEDDylated cofilin regulates actin dynamics.
 Nat Struct Mol Biol, 2020.
27(2): p.
210-220.

8.
Zhao, Y.
and Y.
Sun, Cullin-RING Ligases as Attractive Anti-cancer Targets.
 Curr Pharm Des, 2013.
19(18): p.
3215-25.

9.
Zhou, Q.
, et al.
, Inhibiting neddylation modification alters mitochondrial morphology and reprograms energy metabolism in cancer cells.
 JCI Insight, 2019.
4(4).

Original literature

Neddylation inhibition induces glutamine uptake and metabolism by targeting CRL3SPOP E3 ligase in cancer cells.
 Nature Communications.
2022.

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