Related Experiment Video

Updated: Aug 16, 2026

Merging Absolute and Relative Quantitative PCR Data to Quantify STAT3 Splice Variant Transcripts
11:19

Merging Absolute and Relative Quantitative PCR Data to Quantify STAT3 Splice Variant Transcripts

Published on: October 9, 2016

Nuclear retention of STAT3 through the coiled-coil domain regulates its activity

Noriko Sato1, Rieko Tsuruma, Seiyu Imoto

  • 1Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-Ku Kita 12 Nishi 6, Sapporo 060-0812, Japan.

Biochemical and Biophysical Research Communications
|September 6, 2005
PubMed

Insights

Signal transducer and activator of transcription 3 (STAT3) nuclear export, regulated by Arg-214/215, is crucial for controlling STAT3 activation. This finding clarifies STAT3

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • Signal transducer and activator of transcription 3 (STAT3) is a key transcription factor involved in numerous physiological processes.
  • STAT3 activation involves tyrosine phosphorylation, dimerization, and nuclear translocation, but the precise mechanisms remain incompletely understood.
  • Previous research indicated that mutations in the STAT3 coiled-coil domain (STAT3 RA mutant) impaired nuclear translocation.

Purpose of the Study:

  • To re-examine the function of the STAT3 RA mutant.
  • To elucidate the role of Arg-214/215 in STAT3 nuclear translocation and activity regulation.
  • To investigate the involvement of chromosomal region maintenance 1 (CRM1) in STAT3 nuclear export.

Main Methods:

  • Site-directed mutagenesis to create the STAT3 RA mutant (Arg-214/215 to Alanine).
  • Stimulation of cells with cytokines and growth factors to induce STAT3 activation.
  • Analysis of STAT3 tyrosine phosphorylation levels.
  • Assessment of STAT3 transcriptional activity.
  • Microscopy to observe STAT3 nuclear translocation and export.
  • Treatment with leptomycin B, a CRM1 inhibitor, to block nuclear export.

Main Results:

  • The STAT3 RA mutant exhibited enhanced tyrosine phosphorylation and significantly higher STAT3 transcriptional activity compared to wild-type STAT3.
  • STAT3 RA demonstrated increased nuclear translocation and accelerated nuclear export following stimulation.
  • Inhibition of CRM1-mediated nuclear export using leptomycin B reduced the enhanced STAT3 activation observed with the STAT3 RA mutant.
  • These findings suggest that Arg-214/215 residues are critical for CRM1-mediated nuclear export.

Conclusions:

  • The Arg-214/215 residues in the STAT3 coiled-coil domain are essential regulators of STAT3 nuclear export via CRM1.
  • STAT3 nuclear export plays a significant role in modulating STAT3 transcriptional activity.
  • This study provides novel insights into the regulatory mechanisms governing STAT3 localization and function.

More Related Videos

Describing a Transcription Factor Dependent Regulation of the MicroRNA Transcriptome07:23

Describing a Transcription Factor Dependent Regulation of the MicroRNA Transcriptome

Published on: June 15, 2016

Protein Purification-free Method of Binding Affinity Determination by Microscale Thermophoresis10:22

Protein Purification-free Method of Binding Affinity Determination by Microscale Thermophoresis

Published on: August 15, 2013

Related Concept Videos

The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
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...
Co-activators and Co-repressors02:04

Co-activators and Co-repressors

Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
Co-activators and Co-repressors02:04

Co-activators and Co-repressors

Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
Covalently Linked Protein Regulators02:04

Covalently Linked Protein Regulators

Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein.
Covalently Linked Protein Regulators02:04

Covalently Linked Protein Regulators

Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein.