Related Experiment Video

Updated: May 7, 2026

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
09:18

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death

Published on: December 27, 2016

MADD is a downstream target of PTEN in triggering apoptosis

Shankar Jayarama1, Liang-Cheng Li, Lakshmy Ganesh

  • 1Department of Microbiology and Immunology, College of Medicine, University of Illinois at Chicago, Chicago, Illinois, 60612.

Journal of Cellular Biochemistry
|September 17, 2013
PubMed

Insights

PTEN suppresses cancer cell survival by reducing MADD phosphorylation, which initiates apoptosis. This reveals a new PTEN mechanism in tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) signaling.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Signaling

Background:

  • Mitogen-activated kinase activating death domain containing protein (MADD) promotes cancer cell survival via Akt phosphorylation.
  • PTEN (phosphatase and tensin homolog deleted on chromosome 10) negatively regulates the PI3K-Akt pathway, but its downstream apoptosis targets are unclear.

Purpose of the Study:

  • To investigate the role of PTEN in regulating MADD phosphorylation and its impact on apoptosis.
  • To elucidate the mechanism by which PTEN influences MADD's pro-apoptotic function in TRAIL-induced apoptosis.

Main Methods:

  • Utilized siRNA to knock down PTEN expression.
  • Analyzed MADD phosphorylation levels following TRAIL treatment.
  • Investigated MADD subcellular localization and its interaction with 14-3-3 and Bax using western blotting and microscopy.

Main Results:

  • TRAIL treatment reduced MADD phosphorylation and increased PTEN levels; PTEN knockdown blocked this reduction.
  • PTEN-mediated dephosphorylation caused MADD to translocate from the plasma membrane to the cytoplasm.
  • Cytoplasmic MADD displaced Bax from 14-3-3, leading to Bax mitochondrial translocation and cytochrome c release.

Conclusions:

  • PTEN acts as a crucial mediator of TRAIL-induced apoptosis by inhibiting Akt-mediated MADD phosphorylation.
  • This study identifies a novel PTEN-MADD axis in apoptosis signaling, revealing MADD as a key downstream target.
Keywords:
AKTAPOPTOSISMADDPI3KPTEN

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

LPS and ATP-induced Death of PMA-differentiated THP-1 Macrophages and its Validation06:12

LPS and ATP-induced Death of PMA-differentiated THP-1 Macrophages and its Validation

Published on: May 3, 2024

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...
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...
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...
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.