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 molecule ...

receptor for cargos with leucine-rich nuclear export signals (

NES The Nintendo Entertainment System (NES) is an 8-bit third-generation home video game console produced by Nintendo. It was first released in Japan in 1983 as the commonly known as the The NES, a redesigned version, was released in American ...

). 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 b ...

types and is therefore viewed as a target for development of anti-cancer drugs.

Selinexor Selinexor sold under the brand name Xpovio among others, is a selective inhibitor of nuclear export used as an anti-cancer medication. It works by blocking the action of exportin 1 and thus blocking the transport of several proteins involved i ...

, a drug specifically targeting XPO1, was approved by the

FDA The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...

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 organizati ...

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 prot ...

, *

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 ...

, *

NMD3 60S ribosomal export protein NMD3 is a protein that in humans is encoded by the ''NMD3'' gene. Interactions NMD3 has been shown to interact with XPO1 Exportin 1 (XPO1), also known as chromosomal region maintenance 1 (CRM1), is a eukaryotic pro ...

, *

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 ...

, *

RANBP1 Ran-specific binding protein 1 is an enzyme that in humans is encoded by the ''RANBP1'' gene. Ran/TC4-binding protein, RanBP1, interacts specifically with GTP-charged RAN. RANBP1 encodes a 23-kD protein that binds to RAN complexed with GTP but n ...

, *

RANBP3 Ran-binding protein 3 is a protein that in humans is encoded by the ''RANBP3'' gene. This gene encodes a protein with a RanBD1 domain that is found in both the nucleus and cytoplasm. This protein plays a role in nuclear export as part of a hetero ...

, *

Ran Ran, RaN and ran may refer to: Arts and entertainment * ''Ran'' (film), a 1985 film directed by Akira Kurosawa * "Ran" (song), a 2013 Japanese song by Luna Sea * '' Ran Online'', a 2004 MMORPG (massively multiplayer online role playing game) * ...

, *

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 repressiv ...

, and *

p53 p53, also known as Tumor protein P53, cellular tumor antigen p53 (UniProt name), or transformation-related protein 53 (TRP53) is a regulatory protein that is often mutated in human cancers. The p53 proteins (originally thought to be, and often s ...

References

External links

3D electron microscopy structures of CRM1 from the EM Data Bank(EMDB)
{{Gene-2-stub