Related Experiment Video

Updated: Sep 11, 2025

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

9.6K

The Role of Nuclear Phosphoinositides in the p53-MDM2 Nexus

Jeong Hyo Lee1,2, Muhammad Khalil Salah1,2, Xiangqin Chen1

  • 1University of Wisconsin Carbone Cancer Center, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53705, USA.

Cells
|August 13, 2025
PubMed

Insights

Nuclear phosphoinositides (PIPns) stabilize the tumor suppressor p53 by recruiting small heat shock proteins and activating AKT signaling. These PIPns act as a third messenger in the p53-MDM2 axis, impacting cancer biology.

Area of Science:

  • Molecular Biology
  • Cancer Biology
  • Cell Signaling

Background:

  • The p53-MDM2 pathway is crucial for regulating cell growth and is frequently dysregulated in cancer.
  • Nuclear phosphoinositides (PIPns) are increasingly recognized for their roles in intracellular signaling.
  • Understanding novel regulatory mechanisms of the p53-MDM2 axis is vital for cancer therapy.

Purpose of the Study:

  • To elucidate the molecular mechanisms by which nuclear PIPns modulate the p53-MDM2 interaction.
  • To investigate the role of nuclear PIPns in stabilizing p53 and activating downstream signaling pathways.
  • To establish nuclear PIPns as a key component of non-canonical nuclear signaling in cancer.

Main Methods:

  • Dissection of molecular mechanisms involving nuclear PIPns, p53, MDM2, small heat shock proteins (sHSPs), and the PI3K-AKT pathway.
  • Analysis of signaling coordination between nuclear p53, AKT, and MDM2.
  • Exploration of PIPn-mediated regulation of protein-protein interactions within the nucleus.

Main Results:

  • Nuclear PIPns stabilize p53 through the recruitment of sHSPs.
  • Nuclear PIPns activate the nuclear phosphatidylinositol 3-kinase (PI3K)-AKT signaling cascade.
  • Nuclear PIPns modulate MDM2 function, thereby regulating the p53-MDM2 interaction.

Conclusions:

  • Nuclear PIPns function as a 'third messenger' within the p53-MDM2 axis.
  • Nuclear PIPns expand the understanding of non-canonical nuclear signaling in cancer biology.
  • Targeting nuclear PIPn-mediated signaling may offer novel therapeutic strategies for cancer.
Keywords:
AKTMDM2nucleusp53phosphoinositidesmall heat shock protein

More Related Videos

Purification of Ubiquitinated p53 Proteins from Mammalian Cells10:55

Purification of Ubiquitinated p53 Proteins from Mammalian Cells

Published on: March 21, 2022

2.3K
Identification of Inositol Phosphate or Phosphoinositide Interacting Proteins by Affinity Chromatography Coupled to Western Blot or Mass Spectrometry08:07

Identification of Inositol Phosphate or Phosphoinositide Interacting Proteins by Affinity Chromatography Coupled to Western Blot or Mass Spectrometry

Published on: July 26, 2019

8.6K

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...
4.6K
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...
6.4K
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...
8.7K
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.
35.9K
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...
4.0K
DNA Damage can Stall the Cell Cycle02:37

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...
9.3K