Related Experiment Video

Updated: May 9, 2026

Examining BCL-2 Family Function with Large Unilamellar Vesicles
08:35

Examining BCL-2 Family Function with Large Unilamellar Vesicles

Published on: October 5, 2012

Wip1 suppresses apoptotic cell death through direct dephosphorylation of BAX in response to γ-radiation

J-Y Song1, S-H Ryu, Y M Cho

  • 1Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Asan, Seoul, Korea.

Cell Death & Disease
|August 3, 2013
PubMed

Insights

Wild-type p53-induced phosphatase 1 (Wip1) dephosphorylates BAX, suppressing apoptosis and promoting cancer therapy resistance. This phosphatase activity is crucial for regulating BAX-mediated cell death in response to DNA damage.

Area of Science:

  • Molecular Biology
  • Cancer Biology
  • Biochemistry

Background:

  • Wild-type p53-induced phosphatase 1 (Wip1) is a serine/threonine phosphatase that negatively regulates DNA damage responses.
  • Wip1 is frequently amplified or overexpressed in human tumors, correlating with poor prognosis.
  • Wip1 dephosphorylates key proteins involved in DNA repair and cell cycle checkpoints.

Purpose of the Study:

  • To investigate the role of Wip1 in regulating BAX-mediated apoptosis in prostate cancer cells.
  • To determine if Wip1 directly interacts with and dephosphorylates BAX.
  • To elucidate the mechanism by which Wip1 influences BAX activity and cellular response to radiation therapy.

Main Methods:

  • Co-immunoprecipitation to assess Wip1-BAX interaction.
  • Western blotting to detect protein phosphorylation and levels.
  • γ-irradiation of prostate cancer cells (LNCaP).
  • Use of Wip1 inhibitor and site-directed mutagenesis of BAX.
  • Apoptosis assays in BAX-deficient cells.

Main Results:

  • Wip1 directly interacts with and dephosphorylates BAX at threonines 172, 174, and 186.
  • Radiation-resistant LNCaP cells exhibit increased Wip1 levels and impaired BAX mitochondrial translocation post-irradiation.
  • Wip1 inhibition reversed impaired BAX translocation.
  • Mutations at dephosphorylation sites prevent efficient BAX mitochondrial translocation.
  • Wip1 overexpression, but not phosphatase-dead Wip1, reduces apoptosis in BAX-deficient cells.

Conclusions:

  • Wip1 dephosphorylation of BAX is a novel mechanism that suppresses BAX-mediated apoptosis.
  • This Wip1-mediated downregulation of BAX activity contributes to resistance to anticancer therapies like radiation.
  • Wip1 represents a potential therapeutic target for overcoming treatment resistance in cancer.

More Related Videos

Applying an Inducible Expression System to Study Interference of Bacterial Virulence Factors with Intracellular Signaling08:51

Applying an Inducible Expression System to Study Interference of Bacterial Virulence Factors with Intracellular Signaling

Published on: June 25, 2015

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...
Cellular Injury V: Apoptosis and Autophagy01:22

Cellular Injury V: Apoptosis and Autophagy

Cells respond to damage and stress through highly coordinated processes that decide whether they survive or undergo controlled self-destruction. Two major pathways involved in this regulation are apoptosis, a type of programmed cell death, and autophagy, a survival mechanism that helps cells adapt to adverse conditions.ApoptosisApoptosis removes aged or injured cells to maintain tissue balance. During this process, the cell shrinks, chromatin condenses and fragments, and membrane-bound...
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.
Autophagic Cell Death01:18

Autophagic Cell Death

Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and pro-apoptotic...
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...