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 A genetic screen or mutagenesis screen is an experimental technique used to identify and select individuals who possess a phenotype of interest in a mutagenized population. Hence a genetic screen is a type of phenotypic screen. Genetic screens ...

, 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 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 The subtypes of HIV include two main subtypes, known as HIV type 1 (HIV-1) and HIV type 2 (HIV-2). These subtypes have distinct genetic differences and are associated with different epidemiological patterns and clinical characteristics. HIV-1 e ...

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 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 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 ...

, * NMD3, *

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 ...

, *

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, *

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 ...

, and *

p53 p53, also known as tumor protein p53, cellular tumor antigen p53 (UniProt name), or transformation-related protein 53 (TRP53) is a regulatory transcription factor protein that is often mutated in human cancers. The p53 proteins (originally thou ...

References

External links

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