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
''Schizosaccharomyces pombe'', also called "fission yeast", is a species of yeast used in traditional brewing and as a model organism in molecular and cell biology. It is a unicellular eukaryote, whose cells are rod-shaped. Cells typically meas ...
'' 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 receptor for cargos with
leucine
Leucine (symbol Leu or L) is an essential amino acid that is used in the biosynthesis of proteins. Leucine is an α-amino acid, meaning it contains an α-amino group (which is in the protonated −NH3+ form under biological conditions), an α-Car ...
-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 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 Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...
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 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, ''Cip/Kip'' family of cyclin dependent kinase (Cdk) inhibitor proteins. The enc ...
,CIITA
CIITA is a human gene which encodes a protein called the class II, major histocompatibility complex, transactivator. Mutations in this gene are responsible for the bare lymphocyte syndrome in which the immune system is severely compromised and c ...
,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 repress ...
,
See also
* Karyopherin
Karyopherins are protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme c ...
*Importin
Importin is a type of karyopherin that transports protein molecules from the Eukaryotic Cell, cell's cytoplasm to the cell nucleus, nucleus. It does so by binding to specific recognition sequences, called nuclear localization sequences (NLS).
I ...
* Nuclear transport
* Nuclear export signal
References
Further reading
*
*
*
*
*
External links
3D electron microscopy structures of CRM1 from the EM Data Bank(EMDB)
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