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Comment
. 2022 Jan 6;82(1):13-14.
doi: 10.1016/j.molcel.2021.11.020.

Nuclear destruction: A suicide mission by AKIRIN2 brings intact proteasomes into the nucleus

Xiang Chen  1 , Kylie J Walters  2
Affiliations
Comment

Nuclear destruction: A suicide mission by AKIRIN2 brings intact proteasomes into the nucleus

Xiang Chen et al. Mol Cell. .

Abstract

de Almeida et al. (2021) developed a temporally controlled CRISPR-Cas9 screen to identify mechanisms controlling MYC levels and discovered that intact proteasomes are imported into the nucleus by AKIRIN2 binding to proteasomes at one end and a nuclear import receptor at the other.

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Figures

Figure 1.
Figure 1.. Model of AKIRIN2-mediated proteasome import into the nucleus
In the cytosol, the C-terminal regions of an AKIRIN2 dimer (orange) bind to a proteasome CP (gray) capped at the other end by the RP (blue). IPO9 (green) binds to the N-terminal region of AKIRIN2 and transports the proteasome assembly through the nuclear pore complex (NPC, beige, orange, and green). Once in the nucleus, IPO9 binds to GTP-bound RAN (purple), releasing it from AKIRIN2 and driving its nuclear export. AKIRIN2 is in turn degraded by the CP, providing a binding site for 11Sγ (pink). In the lower panel, key interactions within AKIRIN2 and to the CP are highlighted with hydrogen bonds displayed as black dashed lines. This figure was generated by using PDB entries 7NHT, 5VFS, 6N1Z, 3ZJY, 3GJ0, EMD-3103, and AlphaFold2-predicted AKIRIN2, and a model of human 11Sγ generated by the SWISS-MODEL server.
See this image and copyright information in PMC

Comment on

  • AKIRIN2 controls the nuclear import of proteasomes in vertebrates.
    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 GA, Haselbach D, Zuber J. de Almeida M, et al. Nature. 2021 Nov;599(7885):491-496. doi: 10.1038/s41586-021-04035-8. Epub 2021 Oct 28. Nature. 2021. PMID: 34711951

References

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