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Related Experiment Video

Updated: Jun 25, 2026

Yeast As a Chassis for Developing Functional Assays to Study Human P53

Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

MiR-34, SIRT1 and p53: the feedback loop.

Munekazu Yamakuchi¹, Charles J Lowenstein

¹Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. myamaku1@jhmi.edu

Cell Cycle (Georgetown, Tex.)

|February 18, 2009

Summary

The tumor suppressor p53 activates miR-34a, which inhibits SIRT1. This interaction creates a feedback loop, enhancing p53

Area of Science:

Molecular Biology
Cancer Research
Genetics

Background:

MicroRNAs (miRNAs) are key regulators of gene expression implicated in tumorigenesis.
The TP53 gene, frequently mutated in cancers, encodes p53, which induces miR-34 family members.
The miR-34 family's role in cell cycle, senescence, and apoptosis is established, but targets remain incompletely defined.

Purpose of the Study:

To investigate the functional relationship between miR-34a and SIRT1.
To elucidate the role of SIRT1 in miR-34a-mediated apoptosis.
To propose a novel feedback loop involving p53, miR-34a, and SIRT1 in cancer regulation.

Main Methods:

Investigated the inhibitory effect of miR-34a on SIRT1 expression.
Examined SIRT1's influence on p53 activity and apoptosis.

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Utilized molecular biology techniques to validate the proposed feedback loop.

Main Results:

miR-34a directly inhibits SIRT1, a regulator of cellular senescence and longevity.
SIRT1 deacetylates and stabilizes p53, influencing p53-dependent apoptosis.
SIRT1 mediates miR-34a's apoptotic effects by modulating p53 activity.

Conclusions:

A positive feedback loop exists where p53 induces miR-34a, which suppresses SIRT1, thereby enhancing p53 activity.
This regulatory circuit involving p53, miR-34a, and SIRT1 is crucial for apoptosis and may be a target for cancer therapy.