Related Experiment Video

Updated: Aug 30, 2026

A Guide to Production, Crystallization, and Structure Determination of Human IKK1/α
11:27

A Guide to Production, Crystallization, and Structure Determination of Human IKK1/α

Published on: November 2, 2018

ik3-2, a relative to ik3-1/Cables, is involved in both p53-mediated and p53-independent apoptotic pathways

Masaaki Matsuoka1, Haruka Sudo, Keitaro Tsuji

  • 1Department of Pharmacology, University of KEIO School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. sakimatu@sc.itc.keio.ac.jp

Biochemical and Biophysical Research Communications
|November 26, 2003
PubMed

Insights

The study identifies ik3-2 as a proapoptotic factor. Overexpression of ik3-2 induces apoptosis in cancer cells, both with and without p53, highlighting its role in cell death pathways.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • ik3-2 is related to ik3-1/Cables, a potential tumor suppressor.
  • ik3-1/Cables regulates p53 and p73-induced apoptosis.
  • The role of ik3-2 in apoptosis was previously uncharacterized.

Purpose of the Study:

  • To investigate the role of ik3-2 in apoptosis.
  • To determine if ik3-2 interacts with p53.
  • To elucidate the mechanisms of ik3-2-induced apoptosis.

Main Methods:

  • Adenovirus-mediated overexpression of ik3-2 in U2OS cells and primary mouse embryo fibroblasts.
  • In vivo binding assays to detect ik3-2 and p53 interaction.
  • Analysis of apoptosis in p53-intact and p53-null cells.
  • Domain mapping of ik3-2 to identify regions responsible for apoptosis induction.

Main Results:

  • Overexpression of ik3-2 induces apoptosis in p53-intact U2OS cells.
  • ik3-2 binds to p53 in vivo and enhances p53-induced apoptosis.
  • ik3-2 induces apoptosis in p53/Mdm2- and p53/ARF-null cells, indicating partial p53-independence.
  • The C-terminal (ik3-2-C) and N-terminal (ik3-2-N) domains of ik3-2 contribute to p53-enhanced apoptosis, while ik3-2-N mediates p53-independent apoptosis.

Conclusions:

  • ik3-2 is a proapoptotic factor.
  • ik3-2 participates in both p53-mediated and p53-independent apoptotic pathways.
  • The distinct domains of ik3-2 play specific roles in mediating apoptosis.

More Related Videos

Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation08:47

Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation

Published on: March 5, 2018

Evaluation of Caspase Activation to Assess Innate Immune Cell Death10:23

Evaluation of Caspase Activation to Assess Innate Immune Cell Death

Published on: January 20, 2023

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...
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...
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...
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...
DNA Damage Can Stall the Cell Cycle02:36

DNA Damage Can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
DNA Damage can Stall the Cell Cycle02:36

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...