Today's "Nature": Chinese team to inhibit tumor growth makes new discoveries

Today, the top academic journal "Nature" reported a new research paper from the team of Professor Jiang Hao from the University of Virginia
.

The study found a new mechanism of tumor suppressor protein UTX in cancer suppression, which is expected to bring insights into future cancer treatments

UTX protein is a demethylase of histone H3K27, which acts as a chromatin regulator in cells
.

In terms of specific functions, it can control cell development and differentiation, as well as inhibit the occurrence of cancer

Past studies have found that the most common type of mutation in UTX protein will stop protein synthesis prematurely, causing it to lose the catalytic ability of the demethylase
.

Therefore, many people naturally think that this is the reason why it has lost its ability to suppress cancer

To understand the subsequent findings, let's first get familiar with a concept called "liquid-liquid separation"
.

This term is actually very easy to understand, as if water and oil are both liquids, but if water and oil are mixed together, they will not be perfectly integrated, but will coexist in a separate state.

In cells, the phenomenon of "liquid-liquid separation" is very common
.

Under the action of some proteins, condensates like droplets are formed spontaneously in the cell

This study points out that there is a disordered region (IDR) in the UTX protein, which plays an important role in the formation of these aggregates
.

As for the tumor suppressor effect of UTX protein, it is also indispensable

The researchers did an experiment
.

They reintroduced the UTX protein with this disordered region into cancer cells lacking the UTX gene to restore their ability to form aggregates and promote "liquid-liquid separation"

Interestingly, even disordered regions from other proteins seem to be able to partially reshape the tumor suppressor function of UTX protein
.

These results clearly indicate that "liquid-liquid separation" plays an important role in the tumor suppressor effect of UTX protein

▲Schematic diagram of this research (picture source: reference [2])

Subsequently, the researchers further clarified the underlying mechanism
.
It turns out that after the "liquid-liquid phase separation" occurs, UTX will recruit histone methyltransferase MLL4 into the same aggregate to enhance its function
.
In addition, the histone modification of UTX at the genome level also depends on the occurrence of "liquid-liquid phase separation"
.

In addition, the researchers also found that the UTY homologous protein corresponding to UTX on the Y chromosome has similar functions
.
What's more interesting is that the phase separation ability of UTY is stronger than that of UTX, and the formed agglomerate has less liquidity, and the molecular movement and collision in the UTY agglomerate are also restricted
.
UTY's ability to suppress cancer is therefore lower than that of UTX, which may be one of the reasons why men have a higher rate of cancer than women
.

Taken together, this study shows that tumor suppression is also related to "liquid-liquid separation", and the aggregates formed in this process provide an important physical platform to promote better regulation of chromatin
.

Note: The original text has been deleted

Reference materials:

[1] Shi, B.
, Li, W.
, Song, Y.
et al.
UTX condensation underlies its tumour-suppressive activity.
Nature (2021).
https://doi.
org/10.
1038/s41586-021-03903- 7

[2] Protein condensates provide a platform for controlling chromatin, Retrieved September 15, 2021, from https://