Exportin 1 (XPO1), also known as chromosomal region maintenance 1 (CRM1), is a eukaryotic protein that mediates the nuclear export of various proteins and RNAs.
History
XPO1 (CRM1) originally was identified in the fission yeast ''Schizosaccharomyces pombe'' in a genetic screen, and investigators determined that it was involved in control of the chromosome structure. It was later shown to be the
nuclear transport Nuclear transport refers to the mechanisms by which molecules move across the nuclear membrane of a cell. The entry and exit of large molecules from the cell nucleus is tightly controlled by the nuclear pore complexes (NPCs). Although small molec ...
receptor for cargos with leucine-rich nuclear export signals (
NES). The structural details of the interaction of XPO1 with its cargos were revealed two decades after the gene was identified.
Function
XPO1 mediates NES-dependent protein transport. It exports several hundreds of different proteins from the nucleus. XPO1 is involved in the nuclear export of ribosomal subunits. XPO1 plays a role in export of various RNAs including U snRNAs, rRNAs (as a part of ribosomal subunits), and some mRNAs.
Medical relevance
XPO1 is involved in various viral infections. For example, it is required for the nuclear export of
HIV-1
The subtypes of HIV include two major types, HIV type 1 (HIV-1) and HIV type 2 (HIV-2). HIV-1 is related to viruses found in chimpanzees and gorillas living in western Africa, while HIV-2 viruses are related to viruses found in the sooty mangabey ...
RNA in complex with the viral protein
Rev, an event that is a crucial part of the infection cycle. XPO1 is affected in some
cancer
Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal bl ...
types and is therefore viewed as a target for development of anti-cancer drugs.
Selinexor, a drug specifically targeting XPO1, was approved by the
FDA for treatment of multiple myeloma.
Interactions
XPO1 has been shown to
interact
Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizat ...
with:
*
APC,
[
* ]CDKN1B
Cyclin-dependent kinase inhibitor 1B (p27Kip1) is an enzyme inhibitor that in humans is encoded by the CDKN1B gene. It encodes a protein which belongs to the ''Cip/Kip'' family of cyclin dependent kinase (Cdk) inhibitor proteins. The encoded p ...
,Nucleoporin 62
Nuclear pore glycoprotein p62
is a protein complex associated with the nuclear envelope. The p62 protein remains associated with the nuclear pore complex-lamina fraction. p62 is synthesized as a soluble cytoplasmic precursor of 61 kDa followed by ...
,SMARCB1
SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 is a protein that in humans is encoded by the ''SMARCB1'' gene.
Function
The protein encoded by this gene is part of a complex that relieves repressi ...
,
See also
* Karyopherin
Karyopherins are proteins involved in transporting molecules between the cytoplasm and the nucleus of a eukaryotic cell. The inside of the nucleus is called the karyoplasm (or nucleoplasm). Generally, karyopherin-mediated transport occurs through ...
*Importin
Importin is a type of karyopherin that transports protein molecules from the cell's cytoplasm to the nucleus. It does so by binding to specific recognition sequences, called nuclear localization sequences (NLS).
Importin has two subunits, imp ...
*Nuclear transport Nuclear transport refers to the mechanisms by which molecules move across the nuclear membrane of a cell. The entry and exit of large molecules from the cell nucleus is tightly controlled by the nuclear pore complexes (NPCs). Although small molec ...
*Nuclear export signal
A nuclear export signal (NES) is a short target peptide containing 4 hydrophobic residues in a protein that targets it for export from the cell nucleus to the cytoplasm through the nuclear pore complex using nuclear transport. It has the oppo ...
References
Further reading
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External links
3D electron microscopy structures of CRM1 from the EM Data Bank(EMDB)
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