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Updated: Dec 1, 2025
14:57
Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
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Zmat3 Is a Key Splicing Regulator in the p53 Tumor Suppression Program
Kathryn T Bieging-Rolett1, Alyssa M Kaiser1, David W Morgens2
1Division of Radiation and Cancer Biology, Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Molecular Cell
|November 6, 2020
Summary
Researchers identified Zmat3 (ZMAT3) as a crucial tumor suppressor gene downstream of TP53. ZMAT3 regulates RNA splicing and stability, impacting cancer cell growth and survival.
Area of Science:
- Molecular Biology
- Cancer Research
- Genetics
Background:
- TP53 is frequently mutated in human cancers, but its tumor-suppressive transcriptional targets are not fully understood.
- Identifying downstream effectors of p53 is critical for understanding cancer development and for developing targeted therapies.
Purpose of the Study:
- To uncover novel downstream targets of p53 involved in tumor suppression.
- To investigate the role of the p53-inducible gene Zmat3 (ZMAT3) in cancer.
Main Methods:
- Unbiased in vivo RNAi and CRISPR-Cas9 genetic screens were employed.
- Integrative analysis of ZMAT3's RNA-binding landscape and transcriptomic profiling was performed.
Main Results:
- Screens identified ZMAT3 as a key downstream effector of p53.
- ZMAT3 functions as a tumor suppressor in Kras-driven mouse lung/liver cancers and human carcinomas.
- ZMAT3 directly modulates exon inclusion, affecting transcripts of p53 inhibitors (MDM2, MDM4) and splicing regulators.
- ZMAT3 influences target transcript stability, particularly those with NMD signals.
Conclusions:
- ZMAT3 is a novel regulator of RNA splicing and homeostasis.
- ZMAT3 is a critical component of p53-mediated tumor suppression, offering potential therapeutic targets.
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