Related Experiment Video

Updated: Mar 9, 2026

Yeast As a Chassis for Developing Functional Assays to Study Human P53
14:57

Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

10.1K

Phosphorylated STAT5 regulates p53 expression via BRCA1/BARD1-NPM1 and MDM2

Zhuo Ren1,2,3,4, Joeri L Aerts5, Hugo Vandenplas1,3

  • 1Laboratory of Medical and Molecular Oncology (LMMO), Department of Medical Oncology, Vrije Universiteit Brussel, Brussels, Belgium.

Cell Death & Disease
|December 23, 2016
PubMed

Insights

Signal transducer and activator of transcription 5 (STAT5) directly regulates nucleophosmin 1 (NPM1) expression and phosphorylation. This interaction impacts p53 levels, offering new therapeutic targets for STAT5-driven cancers.

Area of Science:

  • Molecular Biology
  • Cellular Signaling
  • Cancer Biology

Background:

  • Signal transducer and activator of transcription 5 (STAT5) and nucleophosmin 1 (NPM1) are vital regulators in biological and pathological processes.
  • A link between STAT5A and NPM-ALK fusion proteins exists in T-cell lymphoma, but the STAT5 and wild-type NPM1 interaction is uncharacterized.

Purpose of the Study:

  • To elucidate the direct regulatory relationship between STAT5 and NPM1.
  • To investigate the downstream effects of this interaction on p53 expression and cell survival.
  • To identify novel therapeutic targets in STAT5-driven tumors.

Main Methods:

  • Investigated STAT5 phosphorylation (P-STAT5) and its effect on NPM1 expression.
  • Assessed NPM1's regulation of STAT5 phosphorylation and unphosphorylated STAT5 levels.
  • Examined the mechanism of NPM1 downregulation by P-STAT5 involving the BRCA1-BARD1 ubiquitin ligase.
  • Analyzed the impact of NPM1 levels on p53 expression and cell survival.

Main Results:

  • STAT5 phosphorylation (P-STAT5) inversely correlated with NPM1 expression.
  • NPM1 negatively regulated STAT5 phosphorylation and maintained unphosphorylated STAT5.
  • P-STAT5 downregulated NPM1 by impairing BRCA1-BARD1, affecting NPM1 stability.
  • Reduced NPM1 levels suppressed p53, enhancing cell survival.

Conclusions:

  • A novel, mutually regulatory pathway between STAT5 and NPM1 was identified.
  • This pathway regulates p53 expression and influences cell survival.
  • The findings reveal potential therapeutic strategies for cancers involving STAT5 signaling.

More Related Videos

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants07:38

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants

Published on: June 6, 2025

882
Visualization of DNA Repair Proteins Interaction by Immunofluorescence07:55

Visualization of DNA Repair Proteins Interaction by Immunofluorescence

Published on: June 26, 2020

11.3K

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...
5.3K
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...
6.1K
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...
7.6K
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...
10.3K
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...
3.3K
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...
13.5K