The human homologue of yeast CRM1 is in a dynamic subcomplex with CAN/Nup214 and a novel nuclear pore component Nup88.
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.
Fornerod
M
M
Department of Genetics, St Jude Children's Research Hospital, Memphis, TN 38105, USA.
van Deursen
J
J
van Baal
S
S
Reynolds
A
A
Davis
D
D
Murti
K G
KG
Fransen
J
J
Grosveld
G
G
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001755:Blastocyst; D002352:Carrier Proteins / Q000032:analysis / Q000737:chemistry / Q000235:genetics*; D002460:Cell Line; D002467:Cell Nucleus / Q000737:chemistry / Q000378:metabolism; D003001:Cloning, Molecular; D003609:Dactinomycin / Q000494:pharmacology; D005656:Fungal Proteins / Q000032:analysis / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D028884:Karyopherins; D008565:Membrane Proteins / Q000032:analysis / Q000737:chemistry / Q000235:genetics* / Q000302:isolation & purification; D051379:Mice; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009685:Nuclear Envelope / Q000737:chemistry / Q000378:metabolism; D028861:Nuclear Pore Complex Proteins; D009687:Nuclear Proteins / Q000032:analysis / Q000737:chemistry / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism*; D011485:Protein Binding; D012318:RNA Polymerase I / Q000037:antagonists & inhibitors; D018160:Receptors, Cytoplasmic and Nuclear; D012441:Saccharomyces cerevisiae; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D028961:beta Karyopherins; D000097606:Exportin 1 Protein
D002352:Carrier Proteins; D003609:Dactinomycin; D005656:Fungal Proteins; D028884:Karyopherins; D008565:Membrane Proteins; D028861:Nuclear Pore Complex Proteins; D009687:Nuclear Proteins; D012318:RNA Polymerase I; D018160:Receptors, Cytoplasmic and Nuclear; D028961:beta Karyopherins; D000097606:Exportin 1 Protein; C085914:NUP214 protein, human; C104835:NUP88 protein, human; C490093:Nup214 protein, mouse