Liquid-liquid phase separation plays an important role under normal physiological and pathological conditions (1). Protein mutations with the potential for liquid-liquid phase separation are closely related to various diseases such as tumors (2). Among them, a common characteristic mutation of leukemia is a chimeric protein formed by protein with liquid-liquid phase separation potential and a protein with DNA binding ability (3). So how does this chimeric protein play a role in the development of leukemia?
Recently, researchers such as University of North Carolina Gang Greg Wang answered this question very beautifully (4). Researchers found that the chimeric protein composed of liquid phase isolate protein and DNA binding protein can enhance the binding of and gene loci through enhancement and mediate remote interaction to form loops enhance the expression of leukemia-related genes and function to cancer . The mutant liquid-liquid phase separation-dependent site inhibits the subsequent phenotype, and the -independent peptide with liquid-liquid phase separation potential replaces (the non-structural region of the FUS protein used in the article) reproduces the relevant phenotype (4).
researchers said that this may be a more common mechanism for pathogenicity of proteins related to liquid-liquid phase separation (4).
This work was published in nature(4) on June 23, 2021.
Comments:
Functional Compensation Experiment is very convincing and is the highlight of the article. The key to the subsequent key is the universality of the mechanism mentioned in the article; on the other hand, it is the cause of the production of pathogenic chimeric proteins, passive or active processes, and what regulatory mechanisms are there? ;In addition, the specific mechanism of liquid-liquid phase separation of droplets to enhance the expression of related genes is also a question worthy of attention.
chimeric protein composed of liquid-liquid phase isolate and DNA-binding protein mediate loops formation and tumorigenesis (4)
References:
1. S. Alberti, A. A. Hyman, Biomolecularcondensates at the nexus of cellular stress, protein aggregation disease andageing. Nat. Rev. Mol. Cell Biol. 22 (2021), pp. 196–213.
2. A. Boija, I. A. Klein, R. A. Young, Biomolecular Condensates and Cancer. Cancer Cell. 39 (2021), pp.174–192.
3. S. M. Gough, C. I. Slape, P. D. Aplan,NUP98 gene fusions and hematopoietic malignancy: Common themes and new biologic insights. Blood. 118 (2011), pp. 6247–6257.
4. J. H. Ahn et al., Phaseseparation drives aberrant chromatin looping and cancer development. Nature,1–5 (2021).
original link:
https://www.nature.com/articles/s41586-021-03662-5
Note : Originally published on the WeChat public account "CNS Introduction"
on June 24, 2021
