The N-terminal nuclear export sequence of IkappaBalpha is required for RanGTP-dependent binding to CRM1

The Journal of Biological Chemistry
S H Lee, M Hannink

Abstract

Nuclear export of IkappaBalpha is mediated by the CRM1 nuclear export receptor. However, the identity of the nuclear export sequences NES(s) in IkappaBalpha that are responsible for binding of IkappaBalpha to CRM1 is controversial. Both a N-terminal NES-like region (amino acids 45-54) and a C-terminal NES-like region (amino acids 265-280) have, in a number of reports from different laboratories, been implicated in CRM1-dependent nuclear export of IkappaBalpha. We now demonstrate that the N-terminal NES-like region, but not the C-terminal NES-like region, is required for RanGTP-dependent binding of IkappaBalpha to CRM1. IkappaBalpha is a relatively weak substrate for CRM1, with an affinity for CRM1 that is 100-fold less than the minute virus of mice NS2 protein, a high affinity cargo protein for CRM1. We also demonstrate that IkappaBalpha functions as a physical adaptor between CRM1 and NFkappaB/Rel proteins. Both free IkappaBalpha and Rel-associated IkappaBalpha have comparable affinities for CRM1, suggesting that CRM1 does not discriminate between free IkappaBalpha and Rel-associated IkappaBalpha. Nuclear export of c-Rel by IkappaBalpha requires the N-terminal NES-like sequence of IkappaBalpha but is not affected by alanine su...Continue Reading

References

Feb 28, 1995·Proceedings of the National Academy of Sciences of the United States of America·F R BischoffH Ponstingl
Mar 29, 1994·Proceedings of the National Academy of Sciences of the United States of America·F R BischoffH Ponstingl
Jan 1, 1996·Annual Review of Immunology·A S Baldwin
Oct 6, 1997·Science·B Ossareh-NazariC Dargemont
May 23, 1998·Annual Review of Immunology·S GhoshE B Kopp
Dec 5, 1998·The Journal of Biological Chemistry·P AskjaerJ Kjems
Dec 29, 1998·Cell·M D Jacobs, S C Harrison
Apr 20, 1999·The Journal of Cell Biology·E ParaskevaD Görlich
Aug 24, 1999·Molecular and Cellular Biology·P AskjaerM Fornerod
Sep 22, 1999·Molecular and Cellular Biology·E W Harhaj, S C Sun
Feb 3, 2000·Proceedings of the National Academy of Sciences of the United States of America·T T HuangS Miyamoto
Feb 12, 2000·Molecular and Cellular Biology·S SachdevM Hannink

❮ Previous
Next ❯

Citations

Aug 21, 2003·Journal of Biomedical Science·Peter M C Wong, Siu-Wah Chung
May 21, 2005·Nature Reviews. Immunology·Ulrich SiebenlistEstefania Claudio
Aug 16, 2008·Molecular BioSystems·Paul BrennanSaman Hewamana
Apr 16, 2014·Mediators of Inflammation·Ankita Aggarwal, Devendra K Agrawal
Sep 18, 2002·The Journal of Biological Chemistry·Shahana S MahajanAngus C Wilson
Jun 25, 2009·Traffic·Kylie M Wagstaff, David A Jans
Apr 24, 2002·The Journal of Biological Chemistry·Sang-Hyun Lee, Mark Hannink
Aug 11, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Chandra C GhoshIvana Vancurova
Nov 24, 2020·Frontiers in Cell and Developmental Biology·Xiuli WangHongfang Jin
May 13, 2008·Archives of Biochemistry and Biophysics·Hai-Yen VuIvana Vancurova

❮ Previous
Next ❯

Related Concepts

Related Feeds

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.