Related Experiment Video

Updated: Jul 13, 2026

Enhancement of Apoptotic and Autophagic Induction by a Novel Synthetic C-1 Analogue of 7-deoxypancratistatin in Human Breast Adenocarcinoma and Neuroblastoma Cells with Tamoxifen
19:44

Enhancement of Apoptotic and Autophagic Induction by a Novel Synthetic C-1 Analogue of 7-deoxypancratistatin in Human Breast Adenocarcinoma and Neuroblastoma Cells with Tamoxifen

Published on: May 30, 2012

TR4 orphan nuclear receptor functions as an apoptosis modulator via regulation of Bcl-2 gene expression

Eungseok Kim1, Wen-Lung Ma, Din-Lii Lin

  • 1George Whipple Lab for Cancer Research, Department of Pathology, University of Rochester Medical Center, Rochester, NY 14642, USA.

Biochemical and Biophysical Research Communications
|July 28, 2007
PubMed

Insights

The orphan nuclear receptor TR4 modulates apoptosis by upregulating Bcl-2 expression. TR4 deficiency increases susceptibility to UV-induced cell death, impacting Bcl-2 RNA and protein levels.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Genetics

Background:

  • Bcl-2 is crucial for regulating apoptosis.
  • The role of orphan nuclear receptors, like TR4, in apoptosis is not well understood.
  • Understanding TR4's function can reveal new pathways in cell death regulation.

Purpose of the Study:

  • To investigate the role of the orphan nuclear receptor TR4 in apoptosis.
  • To determine if TR4 influences Bcl-2 expression and its impact on UV-induced apoptosis.
  • To explore the interaction of TR4 with coregulators in modulating gene expression.

Main Methods:

  • Comparison of UV-irradiation induced apoptosis in TR4-deficient (TR4(-/-)) and wildtype (TR4(+/+)) mouse embryonic fibroblast (MEF) cells.
  • Analysis of Bcl-2 RNA and protein expression levels.
  • Assessment of caspase-3 activity.
  • Co-transfection experiments with TR4 coregulators, including androgen receptor (AR) and receptor-interacting protein 140 (RIP140).

Main Results:

  • TR4(-/-) MEF cells exhibited increased susceptibility to UV-irradiation mediated apoptosis compared to TR4(+/+) MEF cells.
  • UV-irradiation led to down-regulation of Bcl-2 RNA and protein expression in TR4(-/-) MEF cells, accompanied by increased caspase-3 activity.
  • Co-transfection with AR and RIP140 suppressed TR4-induced Bcl-2 gene expression in a dose-dependent manner.

Conclusions:

  • TR4 functions as a modulator of apoptosis.
  • TR4 induces Bcl-2 gene expression, thereby influencing cell survival and apoptosis.
  • TR4's interaction with coregulators like AR and RIP140 is critical in regulating Bcl-2 expression and apoptosis.

More Related Videos

Preparation of Cell-lines for Conditional Knockdown of Gene Expression and Measurement of the Knockdown Effects on E4orf4-Induced Cell Death13:54

Preparation of Cell-lines for Conditional Knockdown of Gene Expression and Measurement of the Knockdown Effects on E4orf4-Induced Cell Death

Published on: October 21, 2012

Detection of Mitochondria Membrane Potential to Study CLIC4 Knockdown-induced HN4 Cell Apoptosis In Vitro13:20

Detection of Mitochondria Membrane Potential to Study CLIC4 Knockdown-induced HN4 Cell Apoptosis In Vitro

Published on: July 17, 2018

Related Concept Videos

The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
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 activation may...
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 are of three kinds RI, RII, and RIII. The RI...
Apoptosis01:30

Apoptosis

Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size reduction of the tissue.
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...