Researchers such as Jiang Hao from the University of Virginia School of Medicine discovered that a tumor suppressor gene that is frequently mutated in a variety of tumors can function through liquid-liquid phase separation (1).
The protein encoded by this gene is UTX. By deleting, mutating, and replacing its core intrinsically disordered region (cIDR) , researchers found that UTX's inhibitory effect on tumor cells depends on its liquid-liquid phase separation properties, and phase-separated droplets can enrich other chromatin. Modifying proteins jointly change the chromatin state and affect the long-range interaction of DNA by regulating histone methylation.
UTX protein structure and its position responsible for phase separation (1)
UTX protein relies on its disordered region to exert its inhibitory effect on tumor cells (1)
Interestingly, when researchers analyzed the impact of UTX tumor-related mutations on its phase separation properties It was found that some mutations did not weaken its phase separation ability, but made its phase separation droplets worse and solidified. From this, the researchers speculated that the phase separation properties of UTX protein need to be just right to effectively exert the tumor inhibitory effect.
Some tumor-related UTX mutations make UTX droplets less fluid (1)
UTX requires just the right phase separation properties to exert its tumor suppressor function (1)
This work was published in nature on September 15, 2021 (1).
Comments:
It is very difficult to prove that phase separation is the main mechanism of protein function. This article does a more comprehensive job, especially the replacement of intrinsically disordered regions and the analysis of combined patient mutations. However, it should be noted that disordered region replacement does not have a "perfect" recovery phenotype; in addition, whether the enrichment of other chromatin-modifying proteins in phase-separated droplets indeed plays a key role requires further analysis.
Backfilling is not “perfect” (1)
https://www.nature.com/articles/s41586-021-03903-7
Corresponding author introduction:
https://med.virginia.edu/faculty/faculty-listing/hj8d /
Reference:
. B. Shi et al., UTX condensation underlies its tumour-suppressive activity. Nature, 1–6 (2021).
Original link:
https://www.nature.com/articles/s41586- 021-03903-7
