Related Experiment Video

Updated: Jul 9, 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

Interaction with PI3-kinase contributes to the cytotoxic activity of apoptin

S Maddika1, E Wiechec, S R Ande

  • 1Manitoba Institute of Cell Biology, CancerCare Manitoba, University of Manitoba, Winnipeg, Manitoba, Canada.

Oncogene
|December 7, 2007
PubMed

Insights

Apoptin, a viral protein, specifically targets tumor cells. Its interaction with the p85 subunit of phosphoinositide 3-kinase (PI3-K) is crucial for activating cell death pathways in cancer.

Area of Science:

  • Molecular Biology
  • Oncology
  • Virology

Background:

  • Apoptin, a protein from chicken anemia virus, selectively induces apoptosis in tumor cells.
  • Nuclear localization of apoptin is necessary but not sufficient for its tumor-specific cytotoxicity.
  • The precise mechanism underlying apoptin's tumor-killing ability remains incompletely understood.

Purpose of the Study:

  • To elucidate the molecular mechanism by which apoptin induces tumor cell death.
  • To investigate the interaction between apoptin and cellular proteins involved in cell survival pathways.
  • To determine the role of phosphoinositide 3-kinase (PI3-K) signaling in apoptin-mediated apoptosis.

Main Methods:

  • Protein-protein interaction assays to identify apoptin binding partners.
  • Site-directed mutagenesis to map the apoptin interaction domain.
  • Analysis of PI3-K activity in cells expressing apoptin and its mutants.
  • Assessment of apoptosis induction and cell death in cancer cells and normal cells.
  • RNA interference to downregulate p85 expression and evaluate its effect on apoptin activity.

Main Results:

  • Apoptin directly interacts with the SH3 domain of p85, the regulatory subunit of PI3-K, via its proline-rich region.
  • Apoptin mutants lacking the proline-rich region fail to interact with p85, activate PI3-K, or induce apoptosis.
  • Expression of apoptin mutants containing the proline-rich domain restores PI3-K activity and triggers apoptosis in cancer cells.
  • Downregulation of p85 prevents nuclear localization of apoptin and abrogates its cell death-inducing capacity.

Conclusions:

  • The interaction between apoptin and the p85 subunit of PI3-K is essential for apoptin's cytotoxic activity against tumor cells.
  • Apoptin activates PI3-K signaling, leading to apoptosis, and this activation is dependent on its proline-rich region and interaction with p85.
  • Targeting the apoptin-p85 interaction represents a potential therapeutic strategy for cancer treatment.

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

Knockdown of FAM83A to Verify Its Role in Cervical Cancer Cell Growth and Cisplatin Sensitivity04:20

Knockdown of FAM83A to Verify Its Role in Cervical Cancer Cell Growth and Cisplatin Sensitivity

Published on: February 9, 2024

Related Concept Videos

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...
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 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 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...
Phosphoinositides and PIPs01:42

Phosphoinositides and PIPs

Phosphoinositides are a group of phospholipids containing a glycerol backbone with two fatty acid chains and a phosphate attached to a myoinositol sugar ring. The inositol head group extends into the cytoplasm, where it is modified by adding phosphate groups to form phosphatidylinositol phosphates or PIPs.
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
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...