Related Experiment Video

Updated: May 20, 2026

Identification of Nucleolar Factors During HIV-1 Replication Through Rev Immunoprecipitation and Mass Spectrometry
09:38

Identification of Nucleolar Factors During HIV-1 Replication Through Rev Immunoprecipitation and Mass Spectrometry

Published on: June 26, 2019

Identification of ribosomal protein S25 (RPS25)-MDM2-p53 regulatory feedback loop

X Zhang1, W Wang, H Wang

  • 1Department of Pharmaceutical Sciences, Texas Tech University Health Sciences Center, School of Pharmacy, Amarillo, TX 79106, USA.

Oncogene
|July 11, 2012
PubMed

Insights

Ribosomal protein S25 (RPS25) inhibits MDM2-mediated p53 degradation, stabilizing p53. A feedback loop exists where p53 suppresses RPS25 expression, impacting cellular stress response and cancer.

Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Cancer Research

Background:

  • Ribosomal proteins (RPs) are increasingly recognized for roles beyond translation.
  • The MDM2-p53 pathway is crucial for cellular stress response.
  • Dysregulation of this pathway is implicated in cancer development.

Purpose of the Study:

  • To investigate the novel regulatory role of ribosomal protein S25 (RPS25) in the MDM2-p53 pathway.
  • To elucidate the feedback regulation between RPS25 and p53.
  • To understand the implications for cellular stress response and cancer.

Main Methods:

  • Co-immunoprecipitation to assess protein interactions (S25, MDM2, p53, MDMX).
  • Western blotting to analyze protein ubiquitination, stabilization, and activation.
  • siRNA-mediated knockdown of RPS25.
  • Reporter assays to confirm p53 binding to the S25 promoter.

Main Results:

  • RPS25 directly interacts with MDM2, inhibiting its E3 ligase activity and reducing p53 ubiquitination.
  • RPS25 stabilizes p53, leading to its activation, and forms a ternary complex with MDM2 and p53 under ribosomal stress.
  • RPS25 cooperates with MDMX to regulate MDM2 E3 ligase activity.
  • p53 directly binds to the S25 promoter, suppressing its expression, establishing a feedback loop.

Conclusions:

  • RPS25 acts as a novel regulator of the MDM2-p53 pathway by inhibiting p53 degradation.
  • A feedback loop between p53 and RPS25 is identified, suggesting a complex regulatory network.
  • This S25-MDM2-p53 regulatory loop may play a significant role in cancer development and progression.

More Related Videos

Novel RNA-Binding Proteins Isolation by the RaPID Methodology11:19

Novel RNA-Binding Proteins Isolation by the RaPID Methodology

Published on: September 30, 2016

Global Identification of Co-Translational Interaction Networks by Selective Ribosome Profiling06:58

Global Identification of Co-Translational Interaction Networks by Selective Ribosome Profiling

Published on: October 7, 2021

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...
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.
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 rapamycin-insensitive companion...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
Covalently Linked Protein Regulators02:04

Covalently Linked Protein Regulators

Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein.
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...