Related Experiment Video

Updated: Aug 30, 2026

In Vivo Biosensor Tracks Non-apoptotic Caspase Activity in Drosophila
13:21

In Vivo Biosensor Tracks Non-apoptotic Caspase Activity in Drosophila

Published on: November 27, 2016

The Akt-regulated forkhead transcription factor FOXO3a controls endothelial cell viability through modulation of the

Carsten Skurk1, Henrike Maatz, Hyo-Soo Kim

  • 1Molecular Cardiology/Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Massachusetts 02118, USA.

The Journal of Biological Chemistry
|October 11, 2003
PubMed

Insights

The forkhead transcription factor FOXO3a regulates FLIP expression in endothelial cells. FOXO3a activation promotes apoptosis by down-regulating FLIP and activating caspase-8.

Area of Science:

  • Cellular and Molecular Biology
  • Apoptosis Research
  • Endothelial Cell Biology

Background:

  • FLICE-inhibitory protein (FLIP) protects endothelial cells from apoptosis.
  • Akt/PKB kinase promotes FLIP expression in endothelial and tumor cells.

Purpose of the Study:

  • Investigate the role of FOXO3a, a downstream target of Akt, in regulating FLIP in endothelial cells.
  • Elucidate the mechanism by which FOXO3a influences endothelial cell apoptosis via FLIP.

Main Methods:

  • Utilized human umbilical vein endothelial cells.
  • Employed transduction with constitutively active (TM-FOXO3a) and dominant-negative FOXO3a mutants.
  • Assessed FLIP levels, caspase-8 activity, and apoptosis rates.

Main Results:

  • Akt regulated FOXO3a nuclear translocation.
  • Constitutively active FOXO3a down-regulated FLIP, increased caspase-8 activity, and promoted apoptosis.
  • Dominant-negative FOXO3a up-regulated FLIP and conferred protection against apoptosis.
  • Restoring FLIP blocked caspase-8 activation and apoptosis in TM-FOXO3a-transduced cells.

Conclusions:

  • FOXO3a acts downstream of Akt in endothelial cells.
  • FOXO3a promotes apoptosis by down-regulating FLIP and activating the extrinsic apoptotic pathway.

More Related Videos

Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway07:15

Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway

Published on: August 23, 2024

Measuring Composition of CD95 Death-Inducing Signaling Complex and Processing of Procaspase-8 in this Complex07:17

Measuring Composition of CD95 Death-Inducing Signaling Complex and Processing of Procaspase-8 in this Complex

Published on: August 2, 2021

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 hydroxylase and factor...
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...
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...
Caspases01:24

Caspases

Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside cells.
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...
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.