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Related Concept Videos

Nuclear Localization Signals and Import01:46

Nuclear Localization Signals and Import

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...
Regulation of Nuclear Protein Sorting01:45

Regulation of Nuclear Protein Sorting

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...
The Nucleolus02:55

The Nucleolus

The nucleolus is the most prominent substructure of the nucleus. When it was first discovered, it was considered to be an isolated organelle that forms fibrils and granules. In 1931, the relationship between the nucleolus and chromosomes was first described by Heitz. He observed that the appearance and size of nucleolus varies depending on the stage of the cell cycle. He also noticed constricted regions on different chromosomes clustered together at definite cell cycle stages. These regions,...
Nuclear Protein Sorting01:34

Nuclear Protein Sorting

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...
Nuclear Export01:42

Nuclear Export

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.
NES are of three types- the canonical 10-residue long leucine-rich signal and other...
Directionality of Nuclear Transport01:42

Directionality of Nuclear Transport

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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Heterokaryon Technique for Analysis of Cell Type-specific Localization
09:31

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Published on: March 11, 2011

Stat1 nuclear translocation by nucleolin upon monocyte differentiation.

Uwe Jerke1, Sergey Tkachuk, Julia Kiyan

  • 1Hannover Medical School, Hannover, Germany. uwe.jerke@charite.de

Plos One
|December 17, 2009
PubMed
Summary

Nucleolin mediates an alternative pathway for Signal Transducer and Activator of Transcription 1 (Stat1) nuclear import. This novel mechanism is crucial for myeloid cell differentiation, specifically the monocyte-to-macrophage transition.

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Area of Science:

  • Cell Biology
  • Molecular Biology
  • Transcription Factor Regulation

Background:

  • Signal transducer and activator of transcription (Stat) proteins are imported into the nucleus via the nuclear pore complex (NPC).
  • Import can occur through direct binding to nucleoporins or via importin/karyopherin superfamily carriers.
  • Understanding Stat protein nuclear import is critical for cellular regulation.

Purpose of the Study:

  • To investigate an alternative mechanism for Stat1 nuclear import.
  • To identify novel proteins involved in Stat1 translocation.
  • To elucidate the role of this mechanism in myeloid cell differentiation.

Main Methods:

  • Co-immunoprecipitation to detect Stat1-nucleolin association.
  • Confocal microscopy for observing nuclear translocation.
  • Analysis of Stat1 binding to the GAS DNA element.
  • Expression of nucleolin transgenes to identify the functional nuclear localization signal (NLS).

Main Results:

  • Evidence for Stat1-nucleolin complex formation and nuclear import.
  • Stat1-nucleolin complex binds to the GAS regulatory DNA element.
  • The nuclear localization signal (NLS) of nucleolin is essential for Stat1 nuclear translocation.
  • This import pathway is specifically active during monocyte to macrophage differentiation.

Conclusions:

  • Nucleolin acts as a shuttle protein for Stat1 nuclear import via its NLS.
  • The nucleolin-Stat1 complex represents a novel functional partner in cell differentiation.
  • This complex regulates both transcription via Stat1 and nuclear metabolism via nucleolin.