Related Experiment Video

Updated: May 31, 2026

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter
11:32

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter

Published on: March 27, 2020

XIAP-associated factor 1 (XAF1), a novel target of p53, enhances p53-mediated apoptosis via post-translational

Bing Zou1, Chor S Chim, Roberta Pang

  • 1Department of Gastroenterology & Hepatology, The Third Affiliated Hospital of Guangzhou Medical College, Guangzhou, PR China.

Molecular Carcinogenesis
|June 17, 2011
PubMed

Insights

XAF1 (XIAP-associated factor 1) and wild-type p53 form a feedback loop, regulating apoptosis in cancer cells. This interaction impacts p53 activity and XAF1 expression, crucial for cell death pathways.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cellular Biology

Background:

  • The mechanism by which X chromosome-linked inhibitor of apoptosis protein (XIAP)-associated factor 1 (XAF1) mediates apoptosis is not fully understood.
  • Understanding the interplay between XAF1 and key tumor suppressors like p53 is critical for cancer therapy.

Purpose of the Study:

  • To investigate the interaction between XAF1 and wild-type p53.
  • To elucidate the functional significance of this interaction in regulating apoptosis in human gastric and colon cancer cells.

Main Methods:

  • Chromatin immunoprecipitation (CHIP) assay to identify XAF1 as a p53 target gene.
  • Analysis of XAF1 regulation by wild-type and mutant p53 at mRNA and protein levels.
  • Assessment of p53 activation, nuclear accumulation, and transcriptional activity following XAF1 overexpression.

Main Results:

  • Wild-type p53, but not mutant p53, directly down-regulated XAF1 expression via physical interaction with the XAF1 promoter.
  • Overexpression of XAF1 activated wild-type p53 through post-translational modification, leading to increased nuclear accumulation and transcriptional activity.
  • XAF1 overexpression enhanced p53-dependent apoptosis in cancer cells, irrespective of DNA damage.

Conclusions:

  • A novel feedback loop exists between XAF1 and wild-type p53, where they mutually regulate each other's activity and expression.
  • This feedback loop plays a significant role in controlling apoptosis in gastric and colon cancer cells.
  • The findings provide new insights into the molecular mechanisms governing apoptosis and potential therapeutic targets in cancer.

More Related Videos

In Vitro Ubiquitination and Deubiquitination Assays of Nucleosomal Histones11:36

In Vitro Ubiquitination and Deubiquitination Assays of Nucleosomal Histones

Published on: July 25, 2019

Detection of Aggregation-Prone Behavior in Mutant P53 V157F Breast Cancer Cells Using Multipoint Thioflavin T Fluorescence04:56

Detection of Aggregation-Prone Behavior in Mutant P53 V157F Breast Cancer Cells Using Multipoint Thioflavin T Fluorescence

Published on: December 30, 2025

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...
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...
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...
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...