For a detailed description of the NPCs, refer to the previous section on Nuclear Export of RNA.

NPCs are capable of importing and exporting molecules or complexes, provided that the molecules have an exposed nuclear localization signal (NLS) or a nuclear export signal (NES). In Table 1, some of the best-known signals are listed. The NLSs are not cleaved off as occurs for other signals (see later) and thus can function repetitively. Candidates exposing signals for nuclear import (i.e., transcription factors, coactivators or corepressors, DNA repair enzymes, RPs and mRNA processing factors, etc.) or export (ribosomal subunits, mRNA-containing particles, tRNAs, etc.) are transported through the NPC in association with soluble carrier proteins, called karyopherins (also called importins, exportins, or transportins), which function as shuttling receptors for different protein cargos. Ran is a small Ras-like GTPase, belonging to the G protein superfamily, that controls both the docking of carrier proteins with their cargo and the directionality of transport through cycles of GTP binding and hydrolysis.

Table1. Examples of Sorting Signals

NF-κB, a nuclear factor for the transcriptional enhancer of the κ light chain in B lymphocytes and a key element of the stress response, is normally retained in the cytoplasm by interaction with IκB. The TNF-α–dependent phosphorylation of IκB releases NF-κB, thereby exposing an NLS and that allows NF-κB to migrate into the nucleus, where it activates transcription of its target genes. For the glucocorticoid receptor (GR), which is localized in the cytoplasm, binding to its ligand exposes an NLS recognized by an importin and allows translocation into the nucleus, where GR activates genes by bind ing to GR-responsive elements in their promoter regions. The karyopherin export factor XPO1 is overexpressed in a variety of cancer cell types, including multiple myeloma and leukemia. A small molecule inhibitor of XPO1 inhibits the export of leucine-rich NES-dependent proteins, including that of tumor suppressors, such as TP53, TP21, BRCA1/2, pRB, and FOXO, that detect DNA damage in the nucleus and limit cancer cell survival.[1]

References

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[1] Chari A, Vogl DT, Gavriatopoulou M, et al. Oral selinexor dexamethasone for triple-class refractory multiple myeloma. N Engl J Med. 2019;381(8):727–738.

مواضيع ذات صلة

Finding Clones from a Known Amino Acid Sequence

Enzymatic DNA Sequencing

Chemical DNA Sequencing

Ribosome Disorders

The Process of Translation

RNA Granules and Membraneless Organelles

RNA Interference

Balancing Synthesis of Ribosomal Components

Regulation of Ribosome Synthesis

Proportionality of Ribosome Levels and Growth Rates

The Signal Recognition Particle and Translocation

Verifying the Signal Peptide Model