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.
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.
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. [5] It was later shown to be the nuclear transport receptor for cargos with leucine-rich nuclear export signals (NES). [6] [7] [8] [9] The structural details of the interaction of XPO1 with its cargos were revealed two decades after the gene was identified. [10] [11] [12] [13]
XPO1 mediates NES-dependent protein transport. It exports several hundreds of different proteins from the nucleus. [14] [15] XPO1 is involved in the nuclear export of ribosomal subunits. [16] [17] [18] XPO1 plays a role in export of various RNAs including U snRNAs, rRNAs (as a part of ribosomal subunits), and some mRNAs. [19] [20] [21]
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. [22] XPO1 is affected in some cancer types [23] and is therefore viewed as a target for development of anti-cancer drugs. [24] Selinexor, a drug specifically targeting XPO1, was approved by the FDA for treatment of multiple myeloma. [25]
XPO1 has been shown to interact with:
The cell nucleus is a membrane-bound organelle found in eukaryotic cells. Eukaryotic cells usually have a single nucleus, but a few cell types, such as mammalian red blood cells, have no nuclei, and a few others including osteoclasts have many. The main structures making up the nucleus are the nuclear envelope, a double membrane that encloses the entire organelle and isolates its contents from the cellular cytoplasm; and the nuclear matrix, a network within the nucleus that adds mechanical support.
A nuclear pore is a channel as part of the nuclear pore complex (NPC), a large protein complex found in the nuclear envelope in eukaryotic cells, enveloping the cell nucleus containing DNA, which facilitates the selective membrane transport of various molecules across the membrane.
A nuclear localization signalorsequence (NLS) is an amino acid sequence that 'tags' a protein for import into the cell nucleus by nuclear transport. Typically, this signal consists of one or more short sequences of positively charged lysines or arginines exposed on the protein surface. Different nuclear localized proteins may share the same NLS. An NLS has the opposite function of a nuclear export signal (NES), which targets proteins out of the nucleus.
Leptomycins are secondary metabolites produced by Streptomyces spp.
Ribosome biogenesis is the process of making ribosomes. In prokaryotes, this process takes place in the cytoplasm with the transcription of many ribosome gene operons. In eukaryotes, it takes place both in the cytoplasm and in the nucleolus. It involves the coordinated function of over 200 proteins in the synthesis and processing of the three prokaryotic or four eukaryotic rRNAs, as well as assembly of those rRNAs with the ribosomal proteins. Most of the ribosomal proteins fall into various energy-consuming enzyme families including ATP-dependent RNA helicases, AAA-ATPases, GTPases, and kinases. About 60% of a cell's energy is spent on ribosome production and maintenance.
Ran also known as GTP-binding nuclear protein Ran is a protein that in humans is encoded by the RAN gene. Ran is a small 25 kDa protein that is involved in transport into and out of the cell nucleus during interphase and also involved in mitosis. It is a member of the Ras superfamily.
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 molecules can enter the nucleus without regulation, macromolecules such as RNA and proteins require association with transport factors known as nuclear transport receptors, like karyopherins called importins to enter the nucleus and exportins to exit.
The HIV-1 Rev response element (RRE) is a highly structured, ~350 nucleotide RNA segment present in the Env coding region of unspliced and partially spliced viral mRNAs. In the presence of the HIV-1 accessory protein Rev, HIV-1 mRNAs that contain the RRE can be exported from the nucleus to the cytoplasm for downstream events such as translation and virion packaging.
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 modification that involve addition of N-acetylglucosamine residues, followed by association with other complex proteins. In humans it is encoded by the NUP62 gene.
Importin subunit beta-1 is a protein that in humans is encoded by the KPNB1 gene.
Nuclear pore complex protein Nup98-Nup96 is a protein that in humans is encoded by the NUP98 gene.
60S ribosomal protein L5 is a protein that in humans is encoded by the RPL5 gene.
Nucleoporin 153 (Nup153) is a protein which in humans is encoded by the NUP153 gene. It is an essential component of the basket of nuclear pore complexes (NPCs) in vertebrates, and required for the anchoring of NPCs. It also acts as the docking site of an importing karyopherin. On the cytoplasmic side of the NPC, Nup358 fulfills an analogous role.
Transportin-1 is a protein that in humans is encoded by the TNPO1 gene.
Ran-specific binding protein 1 is an enzyme that in humans is encoded by the RANBP1 gene.
Importin-7 is a protein that in humans is encoded by the IPO7 gene.
NTF2-related export protein 1 is a protein that in humans is encoded by the NXT1 gene.
Ran-binding protein 3 is a protein that in humans is encoded by the RANBP3 gene.
60S ribosomal protein L23a is a protein that in humans is encoded by the RPL23A gene.
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 opposite effect of a nuclear localization signal, which targets a protein located in the cytoplasm for import to the nucleus. The NES is recognized and bound by exportins.
PDB gallery | |
|---|---|
|
 | This article on a gene on human chromosome 2 is a stub. You can help Wikipedia by expanding it. |
