7NHT

Akirin2 bound human proteasome

Summary for 7NHT

• Entry DOI: 10.2210/pdb7nht/pdb
• EMDB information: 11649 12341
• Descriptor: Proteasome subunit alpha type-2, Proteasome subunit beta type-2, Proteasome subunit beta type-5, ... (16 entities in total)
• Functional Keywords: proteasome, nuclear import, transport protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 16
• Total formula weight: 425964.11

Authors

Singh, K.,Brunner, H.,Grishkovskaya, I.,de Almeida, M.,Hinterndorfer, M.,Zuber, J.,Haselbach, D. (deposition date: 2021-02-11, release date: 2021-09-01, Last modification date: 2024-07-10)

Primary citation

de Almeida, M.,Hinterndorfer, M.,Brunner, H.,Grishkovskaya, I.,Singh, K.,Schleiffer, A.,Jude, J.,Deswal, S.,Kalis, R.,Vunjak, M.,Lendl, T.,Imre, R.,Roitinger, E.,Neumann, T.,Kandolf, S.,Schutzbier, M.,Mechtler, K.,Versteeg, G.A.,Haselbach, D.,Zuber, J.
AKIRIN2 controls the nuclear import of proteasomes in vertebrates.
Nature, 599:491-496, 2021

PubMed Abstract: Protein expression and turnover are controlled through a complex interplay of transcriptional, post-transcriptional and post-translational mechanisms to enable spatial and temporal regulation of cellular processes. To systematically elucidate such gene regulatory networks, we developed a CRISPR screening assay based on time-controlled Cas9 mutagenesis, intracellular immunostaining and fluorescence-activated cell sorting that enables the identification of regulatory factors independent of their effects on cellular fitness. We pioneered this approach by systematically probing the regulation of the transcription factor MYC, a master regulator of cell growth. Our screens uncover a highly conserved protein, AKIRIN2, that is essentially required for nuclear protein degradation. We found that AKIRIN2 forms homodimers that directly bind to fully assembled 20S proteasomes to mediate their nuclear import. During mitosis, proteasomes are excluded from condensing chromatin and re-imported into newly formed daughter nuclei in a highly dynamic, AKIRIN2-dependent process. Cells undergoing mitosis in the absence of AKIRIN2 become devoid of nuclear proteasomes, rapidly causing accumulation of MYC and other nuclear proteins. Collectively, our study reveals a dedicated pathway controlling the nuclear import of proteasomes in vertebrates and establishes a scalable approach to decipher regulators in essential cellular processes.

PubMed: 34711951
DOI: 10.1038/s41586-021-04035-8

Experimental method

ELECTRON MICROSCOPY (3.2 Å)