Related Experiment Video

Updated: Aug 21, 2026

Detection of Aggregation-Prone Behavior in Mutant P53 V157F Breast Cancer Cells Using Multipoint Thioflavin T Fluorescence
04:56

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

Published on: December 30, 2025

BCR/ABL recruits p53 tumor suppressor protein to induce drug resistance

Tomasz Stoklosa1, Artur Slupianek, Mandrita Datta

  • 1Molecular Carcinogenesis Section, Center of Biotechnology, College of Science and Technology, Temple University, 1900 N. 12th Street, Philadelphia, Pennsylvania 19122, USA.

Cell Cycle (Georgetown, Tex.)
|October 20, 2004
PubMed

Insights

ABL oncoproteins in myeloid leukemia cells use the tumor suppressor p53 to resist DNA damage. This p53 accumulation causes drug resistance and prolonged cell cycle arrest, highlighting a key mechanism in leukemia treatment.

Area of Science:

  • Molecular Biology
  • Oncology
  • Cellular Biology

Background:

  • Tumors with ABL oncoproteins (BCR/ABL, TEL/ABL, v-ABL) resist apoptosis induced by DNA damage.
  • The tumor suppressor p53 is crucial for apoptosis in normal cells but its loss can lead to drug resistance.
  • The interplay between ABL oncoproteins and p53 is critical in understanding oncogenesis and drug resistance.

Purpose of the Study:

  • To investigate the role of p53 in mediating drug resistance in myeloid leukemia cells expressing ABL oncoproteins.
  • To elucidate the mechanism by which ABL oncoproteins influence p53 activity and cellular response to DNA damage.

Main Methods:

  • Analysis of p53 accumulation and caspase-3 activation in ABL oncoprotein-transformed cells versus normal cells after DNA damage.
  • Investigated the role of phosphatidylinositol-3 kinase-like protein kinases (ATR/ATM) in p53 phosphorylation (p53-Ser15).
  • Assessed the impact of p53 inhibition (siRNA, temperature-sensitive mutation) on G(2)/M cell cycle delay and drug resistance.

Main Results:

  • BCR/ABL oncoproteins induced significant p53 accumulation upon DNA damage, unlike normal cells with c-ABL.
  • ATR/ATM-dependent p53 phosphorylation at Ser15 correlated with p53 accumulation, p21(Waf-1)/GADD45 stimulation, and G(2)/M delay.
  • Inhibition of p53 function reversed the G(2)/M accumulation and restored drug sensitivity in BCR/ABL cells.

Conclusions:

  • p53 protein accumulation is a key factor in the prolonged G(2)/M checkpoint activation observed in BCR/ABL-expressing myeloid leukemia cells.
  • The ABL oncoprotein-p53 interaction contributes significantly to drug resistance in myeloid leukemia, offering potential therapeutic targets.

More Related Videos

Silencing of BRCA2 to Identify Novel BRCA2-regulated Biological Functions in Cultured Human Cells09:24

Silencing of BRCA2 to Identify Novel BRCA2-regulated Biological Functions in Cultured Human Cells

Published on: August 12, 2015

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...
Treatment Resistant Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
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...
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.
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...