XPO1

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 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 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 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,
• CIITA,
• NMD3,
• Nucleoporin 62,
• RANBP1,
• RANBP3,
• Ran,
• SMARCB1, and
• p53.

See also

• Karyopherin
• Importin
• Nuclear transport
• Nuclear export signal

External links

• 3D electron microscopy structures of CRM1 from the EM Data Bank(EMDB)