The scientists found that AKIRIN2 was consistently associated with the proteasome and not only required for the regulation of MYC, but of many more short-lived proteins. To their surprise, they found that AKIRIN2 only affected nuclear proteins, which accumulated freely in its absence. Thus, they hypothesised that AKIRIN2 might help the proteasome to enter the nucleus to break down unwanted nuclear proteins.
To test their idea, the team harnessed the IMP’s broad expertise in molecular biology and teamed up with David Haselbach, group leader at the IMP and expert in proteasome biology.
“With our biochemical analyses, we characterised the structure of AKIRIN2, and confirmed that it binds to the proteasome: it forms a dimer that looks a bit like two fingers, which attach to the proteasome and carry it from the cytoplasm into the nucleus,” explains Haselbach. “This process is particularly important after each cell division, where AKIRIN2 quickly imports proteasomes from the cytoplasm into the newly formed nuclei of daughter cells.”
“Our work highlights the power of interdisciplinary research and the collaborative spirit at the IMP. We have this unique setting that brings together researchers from different fields of molecular biology, who then build on each other’s expertise to tackle scientific problems from different angles,” says Zuber.