REDD1 integrates hypoxia-mediated survival signaling downstream of phosphatidylinositol 3-kinase

Related Experiment Video

Updated: Aug 20, 2026

Co-immunoprecipitation Assay Using Endogenous Nuclear Proteins from Cells Cultured Under Hypoxic Conditions
09:17

Co-immunoprecipitation Assay Using Endogenous Nuclear Proteins from Cells Cultured Under Hypoxic Conditions

Published on: August 2, 2018

Rolf Schwarzer1, Daniel Tondera, Wolfgang Arnold

  • 1Atugen AG, Otto Warburg Haus (Nr. 80), Robert-Roessle-Strasse 10, 13125 Berlin, Germany.

Oncogene
|December 14, 2004
PubMed

Insights

REDD1 is a key protein in prostate cancer cells, regulated by PI 3-kinase signaling and hypoxia. It is essential for tumor growth and resistance to apoptosis, making it a potential therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Cell Biology

Background:

  • Cancer cells evade apoptosis through mutations in regulators.
  • Chronic PI 3-kinase-Akt pathway activation, often via PTEN loss, enhances cancer cell survival.
  • Understanding novel regulators of apoptosis evasion is crucial for cancer therapy.

Purpose of the Study:

  • To investigate the role of REDD1 (Regulated in Development and DNA Damage Response 1) in prostate cancer.
  • To determine REDD1's regulation by PI 3-kinase signaling and hypoxia.
  • To assess REDD1's functional significance in prostate cancer cell invasion and apoptosis resistance.

Main Methods:

  • Investigated REDD1 transcriptional regulation in PC-3 prostate cancer cells.
  • Utilized PI 3-kinase inhibitors (LY294002) and mTOR inhibitors (Rapamycin).
  • Examined hypoxia-inducible factor-1 (HIF-1) dependent induction of REDD1.
  • Employed loss-of-function studies (antisense, RNA interference) and overexpression.
  • Assessed apoptosis sensitivity and invasive growth in vitro and in vivo.

Main Results:

  • REDD1 is a transcriptional target of PI 3-kinase signaling in prostate cancer cells.
  • REDD1 expression is decreased by PI 3-kinase/mTOR inhibitors and increased by hypoxia via HIF-1.
  • REDD1 is essential for prostate cancer cell invasion and growth.
  • Altered REDD1 levels modulate apoptosis sensitivity; reduced levels sensitize, while elevated levels desensitize cells to apoptosis.

Conclusions:

  • REDD1 plays a critical role in prostate cancer progression by promoting invasive growth and inhibiting apoptosis.
  • REDD1 is regulated by key cancer-associated signaling pathways (PI 3-kinase, hypoxia).
  • REDD1 represents a promising novel therapeutic target for prostate cancer treatment.

More Related Videos

Induction and Testing of Hypoxia in Cell Culture07:01

Induction and Testing of Hypoxia in Cell Culture

Published on: August 12, 2011

Mechanism of Regulation of Adipocyte Numbers in Adult Organisms Through Differentiation and Apoptosis Homeostasis08:34

Mechanism of Regulation of Adipocyte Numbers in Adult Organisms Through Differentiation and Apoptosis Homeostasis

Published on: June 3, 2016

Related Concept Videos

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 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 hydroxylase and factor...
Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
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...
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...