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Related Concept Videos

Nuclear Protein Sorting01:34

Nuclear Protein Sorting

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Nuclear protein sorting is the selective trafficking of histones, polymerases, gene regulatory proteins into the nucleus and exporting RNAs and ribosomes to the cytosol. It is a tightly controlled process that regulates gene expression within a cell.
Proteins targeted to the nucleus carry nuclear localization signals or NLS recognized by import receptors in the cytosol. Similarly, proteins with nuclear export signals are recognized by export receptors. Import and export receptors are...
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Nuclear Localization Signals and Import01:46

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Proteins targeted to the nucleus carry short stretches of amino acid sequences called the nuclear localization signal or NLS. Classical nuclear localization signals are of two types: monopartite and bipartite NLS. Monopartite classical NLS (cNLS) consists of a single cluster of 4-8 amino acids. Bipartite cNLS consists of two clusters of  2-3 amino acids and a 9-12 residue long proline-rich linker bridging the two clusters. Signal clusters are rich in positively charged amino acids such as...
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Nuclear Export01:42

Nuclear Export

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The nucleus restricts several proteins within and allows others to pass. The restricted proteins possess a nuclear retention sequence or NRS, anchoring them to the nuclear lamins and preventing their transport to the cytosol. The non-restricted proteins, after their synthesis, are transported to their site of action, such as the cytosol or other organelles, with the help of nuclear export signals or NES.
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Directionality of Nuclear Transport01:42

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Ras-related nuclear protein or Ran is a small G protein that cycles between its GTP and GDP bound states. Ran specific regulators, a Ran GTPase Activating Protein or RanGAP present in the cytosol and a Ran guanine nucleotide exchange factor or RanGEF present inside the nucleus regulate GTP/GDP exchange. A high concentration of GTP inside the cells, in addition to this asymmetric distribution of  Ran-specific regulators, leads to a higher RanGTP concentration inside the nucleus. This...
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Regulation of Nuclear Protein Sorting01:45

Regulation of Nuclear Protein Sorting

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Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
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Directing Proteins to the Rough Endoplasmic Reticulum01:34

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The organelle-specific signaling sequences direct proteins synthesized in the cytosol to their final destination like ER, mitochondria, peroxisomes, etc. Some of the proteins directed to ER are then trafficked via vesicles to other organelles within the cell or the extracellular environment through the Golgi complex. For example, the rough ER synthesizes soluble proteins for transportation to the lysosomes or secretion out of the cell. It can also synthesize transmembrane proteins that can...
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Related Experiment Video

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Heterokaryon Technique for Analysis of Cell Type-specific Localization
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A code for RanGDP binding in ankyrin repeats defines a nuclear import pathway.

Min Lu1, Jaroslav Zak1, Shuo Chen1

  • 1Ludwig Institute for Cancer Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, OX3 7DQ, UK.

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|May 27, 2014
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Scientists discovered a new nuclear import pathway for ankyrin repeat proteins (ARPs). A specific code involving hydrophobic residues directs ARPs to the nucleus independently of importins, impacting melanoma and transcriptional regulation.

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Related Experiment Videos

Last Updated: Apr 10, 2026

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Area of Science:

  • Molecular Biology
  • Cell Biology
  • Genetics

Background:

  • Nuclear import is crucial for eukaryotic cell function.
  • Most nuclear proteins use importin-mediated pathways.
  • An importin-independent pathway is needed for proteins lacking importin interaction.

Purpose of the Study:

  • To identify a general importin-independent nuclear import pathway.
  • To define the code governing nuclear import of ankyrin repeat proteins (ARPs).
  • To investigate the role of this pathway in disease and transcriptional regulation.

Main Methods:

  • Identification of a specific amino acid code within ankyrin repeats (ARs).
  • Experimental testing of the code in 17 different ARPs.
  • Prediction of nuclear-cytoplasmic localization for over 150 annotated human ARPs.

Main Results:

  • A hydrophobic residue at position 13 of consecutive ARs mediates efficient binding to RanGDP.
  • This interaction facilitates importin-independent nuclear entry.
  • The identified code accurately predicts ARP localization and is linked to CDKN2A mutations in melanoma.

Conclusions:

  • The RanGDP/AR (RaDAR) pathway is a general importin-independent nuclear import mechanism.
  • This pathway is frequently utilized by ARPs, particularly transcriptional regulators of NF-κB/p53.
  • The discovery has implications for understanding melanoma pathogenesis and gene regulation.