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PMID: 9049309 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

The human homologue of yeast CRM1 is in a dynamic subcomplex with CAN/Nup214 and a novel nuclear pore component Nup88.

The EMBO journal ·Vol. 16 ·No. 4 ·1997-02-17 ·Pages 807-16

Fornerod M, van Deursen J, van Baal S, Reynolds A, Davis D, Murti KG, Fransen J, Grosveld G

Abstract

The oncogenic nucleoporin CAN/Nup214 is essential in vertebrate cells. Its depletion results in defective nuclear protein import, inhibition of messenger RNA export and cell cycle arrest. We recently found that CAN associates with proteins of 88 and 112 kDa, which we have now cloned and characterized. The 88 kDa protein is a novel nuclear pore complex (NPC) component, which we have named Nup88. Depletion of CAN from the NPC results in concomitant loss of Nup88, indicating that the localization of Nup88 to the NPC is dependent on CAN binding. The 112 kDa protein is the human homologue of yeast CRM1, a protein known to be required for maintenance of correct chromosome structure. This human CRM1 (hCRM1) localized to the NPC as well as to the nucleoplasm. Nuclear overexpression of the FG-repeat region of CAN, containing its hCRM1-interaction domain, resulted in depletion of hCRM1 from the NPC. In CAN-/- mouse embryos lacking CAN, hCRM1 remained in the nuclear envelope, suggesting that this protein can also bind to other repeat-containing nucleoporins. Lastly, hCRM1 shares a domain of significant homology with importin-beta, a cytoplasmic transport factor that interacts with nucleoporin repeat regions. We propose that hCRM1 is a soluble nuclear transport factor that interacts with the NPC.

MeSH Terms
Amino Acid Sequence Animals Base Sequence Blastocyst Carrier Proteins/analysis,chemistry,genetics Cell Line Cell Nucleus/chemistry,metabolism Cloning, Molecular Dactinomycin/pharmacology Fungal Proteins/analysis,genetics,isolation & purification Humans Karyopherins Membrane Proteins/analysis,chemistry,genetics,isolation & purification Mice Molecular Sequence Data Molecular Weight Nuclear Envelope/chemistry,metabolism Nuclear Pore Complex Proteins Nuclear Proteins/analysis,chemistry,genetics,isolation & purification,metabolism Protein Binding RNA Polymerase I/antagonists & inhibitors Receptors, Cytoplasmic and Nuclear Saccharomyces cerevisiae Sequence Analysis, DNA Sequence Homology, Amino Acid beta Karyopherins
Chemicals
Carrier Proteins Fungal Proteins Karyopherins Membrane Proteins NUP214 protein, human NUP88 protein, human Nuclear Pore Complex Proteins Nuclear Proteins Nup214 protein, mouse Receptors, Cytoplasmic and Nuclear beta Karyopherins exportin 1 protein Dactinomycin RNA Polymerase I
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Fornerod M
Department of Genetics, St Jude Children's Research Hospital, Memphis, TN 38105, USA.
van Deursen J
van Baal S
Reynolds A
Davis D
Murti K G
Fransen J
Grosveld G
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/16.4.807
Published
1997-02-17
Pages
807-16
Language
English
Region
England
NLM ID
8208664
PMCID
PMC1169681
Subset
IM
Grants
NCI NIH HHS · CA-21765 · United States
Databases
GENBANK
Y08612, Y08613, Y08614
External Links
PubMed source DOI: 10.1093/emboj/16.4.807 PMC Full Text View journal details
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