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Updated: Jun 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

9.5K

Integrative multiomic approaches reveal ZMAT3 and p21 as conserved hubs in the p53 tumor suppression network

Anthony M Boutelle, Aicha R Mabene, David Yao

    Biorxiv : the Preprint Server for Biology
    |September 30, 2024
    PubMed

    Insights

    The tumor suppressor gene TP53

    Area of Science:

    • Oncology
    • Molecular Biology
    • Genetics

    Background:

    • TP53 is the most frequently mutated gene in human cancer.
    • p53 is a transcriptional activator crucial for tumor suppression, but its specific target genes remain unclear.
    • Zmat3 is a p53-inducible gene implicated in tumor suppression, yet its precise role requires further investigation.

    Purpose of the Study:

    • To elucidate the role of Zmat3 in p53-mediated tumor suppression.
    • To identify cooperating p53-inducible genes in tumor suppression.
    • To understand the mechanism of Zmat3 and CDKN1A in opposing tumorigenesis.

    Main Methods:

    • Somatic genome editing and tumor barcoding using Tuba-seq Ultra in a mouse lung adenocarcinoma model.
    • Combinatorial in vivo CRISPR/Cas9 screens.
    • Meta-analyses of gene expression and Cancer Dependency Map data, alongside integrative RNA-sequencing and proteomic analyses.

    Main Results:

    • Zmat3 is confirmed as a core component of p53-mediated tumor suppression.
    • Cdkn1a is identified as the most potent cooperating p53-induced tumor suppressor gene.
    • ZMAT3 and CDKN1A regulate cell division, migration, and extracellular matrix organization, acting as near-universal effectors of p53 tumor suppression.
    • Combined Zmat3-Cdkn1a inactivation significantly enhances cell proliferation and migration, mimicking p53 inactivation.

    Conclusions:

    • ZMAT3 and CDKN1A are key components of a p53-induced gene program that suppresses tumorigenesis.
    • These genes function as hubs in a broader network opposing cancer development.
    • The findings clarify the mechanism of p53-mediated tumor suppression and highlight ZMAT3 and CDKN1A as critical effectors.

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