DOI: 10.1073/pnas.96.20.11370. Autoproteolysis in nucleoporin biogenesis

Autoproteolysis in nucleoporin biogenesis

10.1073/pnas.96.20.11370

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

We have molecularly characterized a proteolytic cleavage in conserved nuclear pore complex proteins. This cleavage, previously demonstrated to be essential for the biogenesis of two nuclear pore complex proteins in mammals (Nup98 and Nup96) and yeast (Nup145-N and Nup145-C), occurs between Phe and Ser residues within a highly conserved domain in a polyprotein precursor. Here, we show that a protease is not involved in the cleavage event. By using a combination of domain mapping and site-directed mutagenesis, we demonstrate that the human nuclear pore complex protein Nup98 specifically cleaves itself between F863 and S864. A region of Nup98, amino acids 715–920, is able to cleave, whereas a smaller region, amino acids 772–920, does not cleave. In addition, we have generated a Nup98 mutant that cleaves under defined conditions in vitro . Further, the two cleaved fragments of Nup98 form a complex, providing a possible mechanism whereby specific, yet low-affinity, binding between Nup98 and Nup96 is responsible for the nuclear targeting of Nup96. Although apparently unrelated evolutionarily, Nup98 has converged on an autoproteolytic biogenesis mechanism similar to that of hedgehog proteins, the inteins, and the N-terminal nucleophile proteins.

Authors 2

Jonathan S. Rosenblum (first)
Günter Blobel (additional)

References 43 Referenced 117

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Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 10:38 a.m.)
Deposited	3 years, 4 months ago (April 13, 2022, 3:51 p.m.)
Indexed	1 month ago (July 25, 2025, 7:01 a.m.)
Issued	25 years, 11 months ago (Sept. 28, 1999)
Published	25 years, 11 months ago (Sept. 28, 1999)
Published Online	25 years, 11 months ago (Sept. 28, 1999)
Published Print	25 years, 11 months ago (Sept. 28, 1999)

Funders 0

None

BibTeX

@article{Rosenblum_1999, title={Autoproteolysis in nucleoporin biogenesis}, volume={96}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.96.20.11370}, DOI={10.1073/pnas.96.20.11370}, number={20}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Rosenblum, Jonathan S. and Blobel, Günter}, year={1999}, month=sep, pages={11370–11375} }

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