Related Experiment Video

Updated: Jul 28, 2026

Isolation of CA1 Nuclear Enriched Fractions from Hippocampal Slices to Study Activity-dependent Nuclear Import of Synapto-nuclear Messenger Proteins
10:03

Isolation of CA1 Nuclear Enriched Fractions from Hippocampal Slices to Study Activity-dependent Nuclear Import of Synapto-nuclear Messenger Proteins

Published on: August 10, 2014

Regulation of Nur77 nuclear export by c-Jun N-terminal kinase and Akt

Y-H Han1, X Cao, B Lin

  • 1Burnham Institute for Medical Research, Cancer Center, La Jolla, CA 92037, USA.

Oncogene
|January 26, 2006
PubMed

Insights

The synthetic retinoid 3-Cl-AHPC triggers apoptosis by causing Nur77 to move from the nucleus to the cytoplasm. This nuclear export is mediated by Jun N-terminal kinase (JNK) activation and Akt inhibition, revealing a key mechanism in apoptosis regulation.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • Nur77, a proapoptotic nuclear receptor, translocates to mitochondria to induce apoptosis.
  • This translocation is triggered by apoptotic stimuli, such as the synthetic retinoid AHPN/CD437 class.
  • Understanding the precise molecular mechanisms of Nur77 translocation is crucial for apoptosis research.

Purpose of the Study:

  • To elucidate the molecular mechanism by which the AHPN/CD437 analog, 3-Cl-AHPC, induces Nur77 nuclear export.
  • To investigate the roles of Jun N-terminal kinase (JNK) and Akt signaling pathways in this process.

Main Methods:

  • Treatment of cells with 3-Cl-AHPC and its analogs.
  • Inhibition of JNK and Akt signaling pathways using specific inhibitors or dominant-negative constructs.
  • Phosphorylation site analysis of Nur77, including mutation of the Akt phosphorylation residue Ser351.
  • Assessment of Nur77 nuclear export and apoptosis induction.

Main Results:

  • 3-Cl-AHPC induced Nur77 nuclear export and apoptosis, dependent on Jun N-terminal kinase (JNK) activation and subsequent Nur77 phosphorylation.
  • Inhibition of JNK suppressed 3-Cl-AHPC-induced Nur77 nuclear export and apoptosis.
  • Akt signaling attenuated MEKK1-induced Nur77 nuclear export, and its inhibition accelerated this process.
  • Mutation of the Akt phosphorylation site (Ser351) on Nur77 abolished the regulatory effect of Akt and PI3-K inhibition.

Conclusions:

  • Both JNK activation and Akt inhibition are critical for the translocation of Nur77 from the nucleus to the cytoplasm.
  • The study reveals a novel signaling pathway involving JNK and Akt in the regulation of Nur77-mediated apoptosis.
  • These findings provide a deeper understanding of the molecular control of apoptosis.

More Related Videos

Production of Nurr-1 Specific Polyclonal Antibodies Free of Cross-reactivity Against Its Close Homologs, Nor1 and Nur7712:30

Production of Nurr-1 Specific Polyclonal Antibodies Free of Cross-reactivity Against Its Close Homologs, Nor1 and Nur77

Published on: August 17, 2015

Study of the Functions and Activities of Neuronal K-Cl Co-Transporter KCC2 Using Western Blotting10:08

Study of the Functions and Activities of Neuronal K-Cl Co-Transporter KCC2 Using Western Blotting

Published on: December 9, 2022

Related Concept Videos

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...
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...
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...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
Regulation of Expression at Multiple Steps01:23

Regulation of Expression at Multiple Steps

The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the addition of a...