How cells import their waste disposal machine into the nucleus

Proteasomes are the cell’s waste disposal machines, breaking down damaged or unwanted proteins to keep cellular processes running smoothly. But to regulate gene activity, proteasomes must also enter the nucleus — a challenge, given their enormous size. Researchers from the labs of David Haselbach and Johannes Zuber at the Research Institute of Molecular Pathology (IMP) now reveal how the adaptor protein AKIRIN2 helps proteasomes gain access to the nucleus, discovering a new principle for transporting large molecular machines. Their findings are published in the journal Nature Communications.

How proteasomes enter the nucleus. AKIRIN2 (green) coats the proteasome (pink) and recruits nuclear transport factors, helping this large molecular machine pass through the nuclear pore (yellow and light brown).

Researchers from the labs of David Haselbach and Johannes Zuber at the IMP, had previously identified the small adaptor protein AKIRIN2 as a key factor required for proteasome import. In a new study, they partnered with collaborators to reveal how AKIRIN2 performs this task at the molecular level, uncovering a new mechanism cells use to move large molecular machines across the nuclear envelope. Their findings are published in the journal Nature Communications.

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Original Publication

H. L. Brunner, R. W. Kalis, L. Grundmann, Z. Hodáková, Z. Koskova, I. Grishkovskaya, M. de Almeida, M. Hinterndorfer, H. Knaudt, S. Höfflin, F. Andersch, H. Kotisch, A. Dickmanns, S. Cuylen-Haering, J. Zuber & D. Haselbach “A multivalent adaptor mechanism drives the nuclear import of proteasomes.” Nature Communications (2026). DOI: 10.1038/s41467-026-69162-0

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