Induction of p73beta by a naphthoquinone analog is mediated by E2F-1 and triggers apoptosis in HeLa cells

Related Experiment Video

Updated: Sep 30, 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

Kyung-Hwa Kang1, Jung-Hee Lee, Keun-Cheol Kim

  • 1Department of Biology, College of Natural Sciences, Chung-Ang University, Heuksuk-dong 221, Dongjak-ku, Seoul 156-756, South Korea.

FEBS Letters
|July 4, 2002
PubMed

Insights

The naphthoquinone analog NA induces apoptosis by increasing p73beta expression and its downstream genes, p21 and bax. This p53-independent pathway involves E2F-1 activation and pRB regulation in HeLa cells.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • p73 is a homolog of p53, regulating gene transcription and apoptosis.
  • Extracellular stimuli and molecular mechanisms controlling p73 activity require further investigation.
  • Understanding p73 regulation is crucial for cancer therapy development.

Purpose of the Study:

  • To identify novel apoptotic stimuli for p73.
  • To elucidate the molecular mechanisms underlying p73 activation by NA.
  • To investigate the role of p73beta in NA-induced apoptosis.

Main Methods:

  • Treatment of HeLa and MCF7 cells with NA.
  • Analysis of p73beta, p21, bax, E2F-1, and pRB expression using mRNA and protein levels.
  • Overexpression studies of p73beta and pRB.

Main Results:

  • NA treatment induced p73beta mRNA and protein expression in HeLa and MCF7 cells.
  • NA upregulated downstream genes p21 and bax, promoting apoptosis.
  • p53 levels decreased in MCF7 cells upon NA treatment.
  • E2F-1 activation, mediated by pRB release, was crucial for p73beta expression.
  • Overexpression of pRB inhibited NA-induced apoptosis.

Conclusions:

  • NA is a novel apoptotic stimulus that activates p73beta.
  • A p53-independent pathway involving p73beta, E2F-1, and p21 mediates NA-induced apoptosis.
  • The p73beta-dependent pathway offers a potential target for cancer treatment.

More Related Videos

Procedure and Key Optimization Strategies for an Automated Capillary Electrophoretic-based Immunoassay Method09:32

Procedure and Key Optimization Strategies for an Automated Capillary Electrophoretic-based Immunoassay Method

Published on: September 10, 2017

Related Concept Videos

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 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...
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
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...
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...