Life activities depend on the spatiotemporal regulation of their proteins. Although this is a very old problem, there is still a lack of technology to study it systematically (1).

2024/04/3023:39:33 science 1234

life activities depend on the spatiotemporal regulation of its proteins. Although this is a very old problem, there is still a lack of technology to study it systematically (1).

Vienna Biocenter, Austria(Vienna Biocenter)Johannes Zuber and David Haselbach and other researchers developed an inducible, or time-controllable, CRISPR screening system to study how the content of nuclear proteins represented by MYC is regulated. (2).

Inducible CRISPR system to screen MYC content-regulating proteins (2)

Researchers found in a variety of cell lines that the content of MYC protein is negatively regulated by the same protein that is highly conserved in vertebrates - AKIRIN2.

AKIRIN2 is a negative regulator of MYC content (2)

Further research found that AKIRIN2 protein binds to the protein degradation machine-proteasome (proteasomes) through its conserved C-terminus, thereby helping the proteasome enter the nucleus to degrade nuclear proteins. effect.

AKIRIN2 helps it enter the nucleus and degrade nuclear proteins by binding to the proteasome (2)

Researchers believe that this work, on the one hand, provides a high-throughput technology for studying how essential genes participate in the regulation of protein content (conventional CRISPR screening will lose essential genes) , on the other hand, has newly revealed a key mechanism for the regulation of protein content in the nucleus of vertebrate cells (2).

This work was published in nature on October 28, 2021.

Comments:

In the future, whole-genome screening technology based directly on degraded proteins will be developed to capture more important information.

In addition, the regulatory mechanism of AKIRIN2 protein under normal physiological and pathological conditions is also worthy of attention.

Corresponding author introduction:

https://www.science.org/content/author/johannes-zuber-md-phd

References:

1. L. Hicke, Protein regulation by monoubiquitin. Nat. Rev. Mol. Cell Biol. 2 , 195–201 (2001).

2. M. de Almeida et al., AKIRIN2 controls the nuclear import of proteasomes in vertebrates. Nature, 1–6 (2021).

Original link:

https://www.nature.com /articles/s41586-021-04035-8

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