The Nucleoporin Nup214 Sequesters Crm1 at the Nuclear Rim and Modulates Nfkappab Activation in Drosophila.
From: Department of Developmental Biology, Wenner-Gren Institute, Stockholm University, S-10691, Stockholm, Sweden.
Journal of cell science
- Publish Date: Nov 2006
- ISSN: 0021-9533
- Volume: 119
- Issue: Pt 21
- Pages: 4409-19
- Medium: Print
- Language: English
- Citation (JAMA): Xylourgidis Nikos, Roth Peggy, Sabri Nafiseh, et al. The Nucleoporin Nup214 Sequesters Crm1 at the Nuclear Rim and Modulates Nfkappab Activation in Drosophila.. J. Cell. Sci. Nov 2006;119:4409-19
Abstract
CRM1-mediated protein export is an important determinant of the nuclear accumulation of many gene regulators. Here, we show that the NFkappaB transcription factor Dorsal is a substrate of CRM1 and requires the nucleoporin Nup214 for its nuclear translocation upon signaling. Nup214 bound to CRM1 directly and anchored it to the nuclear envelope. In nup214 mutants CRM1 accumulated in the nucleus and NES-protein export was enhanced. Nup214 formed complexes with Nup88 and CRM1 in vivo and Nup214 protected Nup88 from degradation at the nuclear rim. In turn, Nup88 was sufficient for targeting the complex to the nuclear pores. Overexpression experiments indicated that Nup214 alone attracts a fraction of CRM1 to the nuclear envelope but does not interfere with NES-GFP export. By contrast, overexpression of the Nup214-Nup88 complex trapped CRM1 and Dorsal to cytoplasmic foci and inhibited protein export and immune response activation. We hypothesize that variation in levels of the Nup214-Nup88 complex at the pore changes the amount of NPC-bound CRM1 and influences the relative strength and duration of NFkappaB signaling responses.
Mesh Headings (Keywords): Active Transport, Cell Nucleus, Animals, Blotting, Western, Cell Nucleus, Cytoplasm, Drosophila Proteins, Drosophila melanogaster, Gene Expression Regulation, Developmental, Green Fluorescent Proteins, Immunoprecipitation, Karyopherins, Larva, Mutagenesis, Site-Directed, Mutation, NF-kappa B, Nuclear Envelope, Nuclear Localization Signals, Nuclear Pore, Nuclear Pore Complex Proteins, Protein Transport, RNA, Small Interfering, Receptors, Cytoplasmic and Nuclear
Check for Full Text / PubMed Unique Identifier (PMID): 17032737
This abstract is part of PubMed, a service of the U.S. National Library of Medicine. PubMed includes more than 17 million citations from MEDLINE and other life science journals for biomedical articles. See Copyright and Disclaimers.
Linked medical terms appearing on this page are added by Healia to help readers find more information and are not part of the original PubMed document.
The data herein was last updated on July 8th, 2008 and may not reflect the most current and accurate data available from NLM.