Related Experiment Video
Updated: Mar 10, 2026
Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
Molecular Mechanisms of p53 Deregulation in Cancer: An Overview in Multiple Myeloma
Ana B Herrero1,2, Elizabeta A Rojas3,4, Irena Misiewicz-Krzeminska5,6,7
1Cancer Research Center-IBMCC (USAL-CSIC), 37007 Salamanca, Spain. anah@usal.es.
Abstract:
The p53 pathway is inactivated in the majority of human cancers. Although this perturbation frequently occurs through the mutation or deletion of p53 itself, there are other mechanisms that can attenuate the pathway and contribute to tumorigenesis. For example, overexpression of important p53 negative regulators, such as murine double minute 2 (MDM2) or murine double minute 4 (MDM4), epigenetic deregulation, or even alterations in TP53 mRNA splicing. In this work, we will review the different mechanisms of p53 pathway inhibition in cancer with special focus on multiple myeloma (MM), the second most common hematological malignancy, with low incidence of p53 mutations/deletions but growing evidence of indirect p53 pathway deregulation. Translational implications for MM and cancer prognosis and treatment are also reviewed.
Insights
The p53 pathway, crucial for preventing cancer, is often inactivated through various mechanisms beyond direct mutation. This review focuses on how p53 pathway inhibition contributes to multiple myeloma and other cancers.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Genetics
Background:
- The p53 pathway is a critical tumor suppressor pathway frequently disrupted in human cancers.
- While p53 mutations/deletions are common, other mechanisms also lead to pathway inactivation.
- Multiple myeloma (MM) shows low rates of direct p53 alteration but exhibits indirect pathway deregulation.
Purpose of the Study:
- To review diverse mechanisms of p53 pathway inhibition in cancer.
- To specifically examine p53 pathway deregulation in multiple myeloma.
- To discuss translational implications for cancer prognosis and treatment.
Main Methods:
- Literature review of p53 pathway regulation and inactivation mechanisms.
- Focus on studies investigating p53 pathway alterations in multiple myeloma.
- Analysis of translational research on p53 in cancer therapy.
Main Results:
- p53 pathway inhibition occurs via direct mutation/deletion or indirect mechanisms like overexpression of negative regulators (MDM2, MDM4), epigenetic changes, and altered mRNA splicing.
- Indirect p53 pathway deregulation is increasingly recognized in multiple myeloma.
- Understanding these mechanisms offers potential therapeutic targets.
Conclusions:
- The p53 pathway is inactivated through multiple mechanisms in cancer, including indirect routes relevant to multiple myeloma.
- Targeting p53 pathway regulators presents a promising therapeutic strategy for MM and other cancers.
- Further research into indirect p53 inhibition is crucial for improving cancer treatment and prognosis.
More Related Videos
04:56Detection of Aggregation-Prone Behavior in Mutant P53 V157F Breast Cancer Cells Using Multipoint Thioflavin T Fluorescence
Published on: December 30, 2025
05:32Multimodal Bioluminescent and Positronic-emission Tomography/Computational Tomography Imaging of Multiple Myeloma Bone Marrow Xenografts in NOG Mice
Published on: January 7, 2019
Related Concept Videos
02:23Abnormal Proliferation
01:19Interactions Between Signaling Pathways
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...
01:31The Intrinsic Apoptotic Pathway
02:36DNA Damage can Stall the Cell Cycle
02:36DNA Damage Can Stall the Cell Cycle
02:04Covalently Linked Protein Regulators
These groups modify specific amino acids in a protein....