Exploiting AKIRIN2 to develop selective proteasome-inhibiting drugs

Inhibitors that block the activity of the proteasome are already applied to treat various types of cancer. However, existing drugs affect proteasomes in all the cells of our body, which can lead to unwanted side-effects in healthy cells.

“Our study shows that AKIRIN2 is required for bringing proteasomes into the nucleus after each cell division. Drugs blocking the interaction between AKIRIN2 and the proteasome could therefore provide a strategy to selectively inhibit nuclear proteasomes in rapidly dividing cells, such as cancer cells,” says Matthias Hinterndorfer.

To develop such selective proteasome inhibitors, scientists need to better understand how AKIRIN2 functions and how it is regulated. Luckily, the assay that the team pioneered in this study is applicable to virtually any gene – and now can be used to uncover the factors that regulate AKIRIN2.

“Our paper represents a fundamental discovery for biology, but it’s also a major technical advancement for the study of gene regulatory networks,” says de Almeida. “Our assay may allow scientists to study essential regulators of any protein of interest, including proteins that are related to cancer.”

The ground-breaking study combines the development of a novel assay to study essential regulatory pathways in the cell, the discovery of an essential regulator of nuclear proteins, and the characterisation of its 3-dimensional structure.