Supraphysiological nuclear export signals bind CRM1 independently of RanGTP and arrest at Nup358

Dieuwke Engelsma, Rafael Bernad, Jero Calafat, Maarten Fornerod*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

81 Citations (Scopus)


Leucine-rich nuclear export signals (NESs) mediate rapid nuclear export of proteins via interaction with CRM1. This interaction is stimulated by RanGTP but remains of a relatively low affinity. In order to identify strong signals, we screened a 15-mer random peptide library for CRM1 binding, both in the presence and absence of RanGTP. Under each condition, strikingly similar signals were enriched, conforming to the NES consensus sequence. A derivative of an NES selected in the absence of RanGTP exhibits very high affinity for CRM1 in vitro and stably binds without the requirement of RanGTP. Localisation studies and RNA interference demonstrate inefficient CRM1-mediated export and accumulation of CRM1 complexed with the high-affinity NES at nucleoporin Nup358. These results provide in vivo evidence for a nuclear export reaction intermediate. They suggest that NESs have evolved to maintain low affinity for CRM1 to allow efficient export complex disassembly and release from Nup358.

Original languageEnglish
Pages (from-to)3643-3652
Number of pages10
JournalEMBO Journal
Issue number18
Publication statusPublished - 26 Aug 2004
Externally publishedYes


Dive into the research topics of 'Supraphysiological nuclear export signals bind CRM1 independently of RanGTP and arrest at Nup358'. Together they form a unique fingerprint.

Cite this