Related Experiment Video

Updated: Jun 29, 2025

A Chromatin Immunoprecipitation Assay to Identify Novel NFAT2 Target Genes in Chronic Lymphocytic Leukemia
09:52

A Chromatin Immunoprecipitation Assay to Identify Novel NFAT2 Target Genes in Chronic Lymphocytic Leukemia

Published on: December 4, 2018

7.5K

Targeting the chromatin binding of exportin-1 disrupts NFAT and T cell activation

Yi Fan Chen1,2, Maryam Ghazala1,2, Ryan M Friedrich1,2

  • 1Department of Genetics and Genome Sciences, Case Western Reserve University School of Medicine, Cleveland, OH, USA.

Nature Chemical Biology
|March 26, 2024
PubMed

Insights

Exportin-1 (XPO1) is crucial for T cell activation by binding to chromatin. New XPO1 modulators target this function, offering therapeutic potential beyond cancer, including for autoimmune disorders.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Immunology

Background:

  • Exportin-1 (XPO1/CRM1) mediates nuclear export and has roles in cell division.
  • XPO1 inhibitors like selinexor are FDA-approved for cancer therapy.
  • The precise role of XPO1 in T cell activation remained unclear.

Purpose of the Study:

  • To investigate the role of XPO1 in T cell activation.
  • To identify novel XPO1 modulators with a distinct mechanism of action.

Main Methods:

  • Chromatin immunoprecipitation assays to assess XPO1 binding.
  • T cell activation assays.
  • Development and testing of novel small molecule inhibitors.

Main Results:

  • XPO1 exhibits a cell-type-dependent chromatin-binding function essential for T cell activation.
  • XPO1 chromatin binding is required for NFAT transcription factor occupancy.
  • A new class of XPO1 modulators was identified that disrupts XPO1 chromatin binding without affecting nuclear export or causing cytotoxicity.

Conclusions:

  • XPO1 plays a significant role in regulating T cell activation through chromatin binding.
  • Novel XPO1 modulators offer a therapeutic strategy for T cell-driven autoimmune disorders, distinct from current oncology treatments.

More Related Videos

Chromatin Immunoprecipitation ChIP to Assay Dynamic Histone Modification in Activated Gene Expression in Human Cells13:20

Chromatin Immunoprecipitation ChIP to Assay Dynamic Histone Modification in Activated Gene Expression in Human Cells

Published on: July 29, 2010

28.7K
NF-κB-dependent Luciferase Activation and Quantification of Gene Expression in Salmonella Infected Tissue Culture Cells10:57

NF-κB-dependent Luciferase Activation and Quantification of Gene Expression in Salmonella Infected Tissue Culture Cells

Published on: January 12, 2020

10.6K

Related Concept Videos

NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
7.4K
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...
3.6K
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...
7.3K
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...
2.4K
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...
3.2K
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...
4.6K