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Differential recognition of canonical NF-κB dimers by Importin α3.

ABSTRACT: Nuclear translocation of the p50/p65 heterodimer is essential for NF-κB signaling. In unstimulated cells, p50/p65 is retained by the inhibitor IκBα in the cytoplasm that masks the p65-nuclear localization sequence (NLS). Upon activation, p50/p65 is translocated into the nucleus by the adapter importin α3 and the receptor importin β. Here, we describe a bipartite NLS in p50/p65, analogous to nucleoplasmin NLS but exposed in trans. Importin α3 accommodates the p50- and p65-NLSs at the major and minor NLS-binding pockets, respectively. The p50-NLS is the predominant binding determinant, while the p65-NLS induces a conformational change in the Armadillo 7 of importin α3 that stabilizes a helical conformation of the p65-NLS. Neither conformational change was observed for importin α1, which makes fewer bonds with the p50/p65 NLSs, explaining the preference for α3. We propose that importin α3 discriminates between the transcriptionally active p50/p65 heterodimer and p50/p50 and p65/65 homodimers, ensuring fidelity in NF-κB signaling.

SUBMITTER: Florio TJ

PROVIDER: S-EPMC8904830 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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Differential recognition of canonical NF-κB dimers by Importin α3.

Florio Tyler J TJ Lokareddy Ravi K RK Yeggoni Daniel P DP Sankhala Rajeshwer S RS Ott Connor A CA Gillilan Richard E RE Cingolani Gino G

Nature communications 20220308 1

Nuclear translocation of the p50/p65 heterodimer is essential for NF-κB signaling. In unstimulated cells, p50/p65 is retained by the inhibitor IκBα in the cytoplasm that masks the p65-nuclear localization sequence (NLS). Upon activation, p50/p65 is translocated into the nucleus by the adapter importin α3 and the receptor importin β. Here, we describe a bipartite NLS in p50/p65, analogous to nucleoplasmin NLS but exposed in trans. Importin α3 accommodates the p50- and p65-NLSs at the major and mi ...[more]

PMID: 35260573

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Dataset Information

Differential recognition of canonical NF-κB dimers by Importin α3.

Publications

Differential recognition of canonical NF-κB dimers by Importin α3.

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