Related Experiment Video

Updated: Apr 25, 2026

Author Spotlight: Investigating Physiological Functions of Vitamin A Transporters Using HPLC-Based Vitamin A Profiling
05:03

Author Spotlight: Investigating Physiological Functions of Vitamin A Transporters Using HPLC-Based Vitamin A Profiling

Published on: December 27, 2024

1.7K

AEG-1 regulates retinoid X receptor and inhibits retinoid signaling

Jyoti Srivastava1, Chadia L Robertson2, Devaraja Rajasekaran1

  • 1Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, Virginia.

Cancer Research
|August 16, 2014
PubMed

Insights

Astrocyte-elevated gene-1 (AEG-1) interacts with Retinoid X receptor (RXR), inhibiting its function and promoting cancer cell survival. Targeting AEG-1 may enhance cancer therapy effectiveness.

Area of Science:

  • Molecular Biology
  • Oncology
  • Cellular Biology

Background:

  • Retinoid X receptor (RXR) plays a crucial role in cell growth and development, but its regulation is often disrupted in cancers like hepatocellular carcinoma (HCC).
  • The specific molecules responsible for RXR deregulation in cancer remain largely unidentified.

Purpose of the Study:

  • To identify molecules that interact with and regulate RXR function in cancer.
  • To investigate the role of astrocyte-elevated gene-1 (AEG-1) in RXR deregulation and its impact on cancer cell survival and proliferation.

Main Methods:

  • Identified RXR as an interacting partner of AEG-1 using co-immunoprecipitation and Western blotting.
  • Assessed the effect of AEG-1 on RXR/retinoic acid receptor (RAR)-mediated transcriptional activation using reporter gene assays.
  • Examined the subcellular localization of RXR and AEG-1 in different cell types via immunofluorescence microscopy.
  • Investigated the role of ERK signaling in AEG-1-mediated RXR phosphorylation using Western blotting and kinase assays.
  • Evaluated the therapeutic potential of combining all-trans retinoic acid (ATRA) with AEG-1 knockdown in a human HCC xenograft mouse model.

Main Results:

  • AEG-1 directly interacts with RXR and inhibits RXR/RAR-mediated transcription.
  • AEG-1 confers resistance to retinoid- and rexinoid-induced cell death in HCC and acute myelogenous leukemia (AML) cells.
  • AEG-1 alters RXR localization (cytoplasmic entrapment in tumor cells) and promotes RXR phosphorylation by ERK, leading to functional inactivation.
  • Combined ATRA treatment and AEG-1 knockdown synergistically inhibited HCC xenograft growth in vivo.

Conclusions:

  • AEG-1 is a novel regulator of RXR and RXR/RAR activity, contributing to hepatocarcinogenesis.
  • AEG-1-mediated RXR inhibition represents a potential therapeutic vulnerability in HCC and AML.
  • Targeting AEG-1 could sensitize cancer patients to retinoid- and rexinoid-based therapies.

More Related Videos

Author Spotlight: Unraveling Vitamin A Transport Mechanisms — Linking Liver Receptors to Vision Health Through RBPR2 and RBP4 Interactions08:18

Author Spotlight: Unraveling Vitamin A Transport Mechanisms — Linking Liver Receptors to Vision Health Through RBPR2 and RBP4 Interactions

Published on: October 4, 2024

1.4K
Prediction and Validation of Gene Regulatory Elements Activated During Retinoic Acid Induced Embryonic Stem Cell Differentiation09:07

Prediction and Validation of Gene Regulatory Elements Activated During Retinoic Acid Induced Embryonic Stem Cell Differentiation

Published on: June 21, 2016

7.6K

Related Concept Videos

Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.9K
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR...
2.0K
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
7.1K
Eukaryotic Transcription Inhibitors01:52

Eukaryotic Transcription Inhibitors

Certain biochemical processes, such as embryonic development and cell growth regulation, depend on the repression of specific genes. DNA binding proteins known as eukaryotic transcription inhibitors regulate the repression of gene expression in eukaryotes. The presence of these inhibitors at the required location and time in the cell is triggered by the presence of hormones and additional signals from other cells.
Eukaryotic transcription inhibitors usually contain two distinct domains, a...
9.0K
Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal01:22

Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal

Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.
1.8K
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
32.1K