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Related Concept Videos

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...
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 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...
Histone Modification02:32

Histone Modification

The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
Histone Modification02:32

Histone Modification

The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
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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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Related Experiment Video

Updated: Jul 9, 2026

Examination of Proteins Bound to Nascent DNA in Mammalian Cells Using BrdU-ChIP-Slot-Western Technique
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PP2A regulates HDAC4 nuclear import.

Gabriela Paroni1, Nadia Cernotta, Claudio Dello Russo

  • 1Dipartimento di Scienze e Tecnologie Biomediche, Sezione di Biologia and MATI Center of Excellence, Universita' di Udine, 33100 Udine, Italy.

Molecular Biology of the Cell
|November 30, 2007
PubMed
Summary

Protein phosphatase 2A (PP2A) dephosphorylates histone deacetylase 4 (HDAC4), promoting its nuclear entry. This dephosphorylation is crucial for regulating gene repression by class II HDACs.

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Last Updated: Jul 9, 2026

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Published on: January 14, 2016

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Assays for Validating Histone Acetyltransferase Inhibitors
09:11

Assays for Validating Histone Acetyltransferase Inhibitors

Published on: August 6, 2020

Area of Science:

  • Molecular Biology
  • Epigenetics
  • Cell Biology

Background:

  • Class II histone deacetylases (HDACs) regulate gene transcription through phosphorylation-dependent nuclear export.
  • Mechanisms controlling the nuclear import and gene repression activity of class II HDACs remain largely unknown.
  • Phosphatases are hypothesized to play a role in promoting nuclear entry of class II HDACs.

Purpose of the Study:

  • To investigate the role of phosphatases in the nuclear import of class II HDACs.
  • To identify the specific phosphatase involved in regulating HDAC4 nuclear localization.
  • To elucidate the molecular mechanisms by which PP2A controls HDAC4 nuclear entry.

Main Methods:

  • Co-immunoprecipitation assays to detect protein complex formation.
  • In vitro and in vivo binding studies to map interaction domains.
  • Treatment with okadaic acid (a PP2A inhibitor) and RNA interference to assess PP2A's role.
  • Site-directed mutagenesis to investigate the function of serine 298.

Main Results:

  • HDAC4 forms a stable complex with the PP2A holoenzyme.
  • The N-terminus of HDAC4 interacts with the catalytic subunit of PP2A.
  • PP2A dephosphorylates HDAC4, promoting its nuclear import.
  • Serine 298 is identified as a critical site for HDAC4 nuclear import; mimicking its phosphorylation impairs import.
  • Mutation of serine 298 partially restores nuclear import in PP2A-depleted cells.

Conclusions:

  • Protein phosphatase 2A (PP2A) directly interacts with and dephosphorylates HDAC4.
  • PP2A-mediated dephosphorylation of HDAC4, including at serine 298, is essential for its nuclear import.
  • This mechanism links PP2A activity to the regulation of gene repression by class II HDACs.