A multivalent adaptor mechanism drives the nuclear import of proteasomes

Nuclear protein homeostasis, including transcription factor turnover, critically depends on the nuclear proteasomes that must be imported after cell division. This dynamic process requires AKIRIN2, a small unstructured protein whose mechanistic role has remained elusive despite its essential function. Using an integrated approach combining protein-wide saturation mutagenesis screens, cryo-EM, and biochemical reconstitution, we characterize AKIRIN2 as a scaffold protein that coordinates the assembly of an importin cluster around the proteasome. AKIRIN2 binds in multiple copies to the 20S proteasome and simultaneously interacts with importin IPO9 and the KPNA2/KPNB1 heterodimer. In the nucleus, RanGTP triggers importin dissociation, releasing the proteasome, while AKIRIN2 undergoes ubiquitin-independent degradation. Our findings reveal how AKIRIN2's multivalency facilitates the recruitment of multiple importins to the proteasome, a critical adaptation for transporting this large macromolecular complex into the nucleus and maintaining the nuclear proteome.

Authors

Institutions

Publication Details

Journal
Nature Communications
Published
2026-02-04
DOI
https://doi.org/10.1038/s41467-026-69162-0
Primary Topic
Ubiquitin and proteasome pathways
Type
article
Field-Weighted Citation Impact
0.00
Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

A multivalent adaptor mechanism drives the nuclear import of proteasomes

Hanna L. Brunner, Zuzana Hodáková, Robert Kalis, Zuzana Koskova et al.
Nature Communications
Ubiquitin and proteasome pathways
article

A multivalent adaptor mechanism drives the nuclear import of proteasomes

Hanna L. Brunner, Zuzana Hodáková, Robert Kalis, Zuzana Koskova, Irina Grishkovskaya, Lorenz Grundmann, Florian Andersch, Achim Dickmanns, Melanie de Almeida, Matthias Hinterndorfer, Hannah Knaudt, Simon Höfflin, Harald Kotisch, Sara Cuylen-Haering, Johannes Zuber
article en

Abstract

Nuclear protein homeostasis, including transcription factor turnover, critically depends on the nuclear proteasomes that must be imported after cell division. This dynamic process requires AKIRIN2, a small unstructured protein whose mechanistic role has remained elusive despite its essential function. Using an integrated approach combining protein-wide saturation mutagenesis screens, cryo-EM, and biochemical reconstitution, we characterize AKIRIN2 as a scaffold protein that coordinates the assembly of an importin cluster around the proteasome. AKIRIN2 binds in multiple copies to the 20S proteasome and simultaneously interacts with importin IPO9 and the KPNA2/KPNB1 heterodimer. In the nucleus, RanGTP triggers importin dissociation, releasing the proteasome, while AKIRIN2 undergoes ubiquitin-independent degradation. Our findings reveal how AKIRIN2's multivalency facilitates the recruitment of multiple importins to the proteasome, a critical adaptation for transporting this large macromolecular complex into the nucleus and maintaining the nuclear proteome.

Nature CommunicationsVol. 17(1)
Broad Institute (US), Research Institute of Molecular Pathology (AT), Dana-Farber Cancer Institute (US), European Molecular Biology Laboratory (DE), Vienna Biocenter (AT), University of Göttingen (DE), Medical University of Vienna (AT)
Openalex Percentile: Top 68%
Ubiquitin and proteasome pathways
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.