Related Experiment Video

Updated: Jun 21, 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

Functional consequences of a p53-MDM2-p21 incoherent feedforward loop

Jamie A Dean, Jose Reyes, Michael Tsabar

    Biorxiv : the Preprint Server for Biology
    |July 9, 2024
    PubMed

    Insights

    Cancer cells show varied responses to treatment. Researchers found p21 expression depends on p53 changes, revealing a regulatory loop that influences cell cycle arrest and treatment tolerance.

    Area of Science:

    • Cellular biology
    • Cancer research
    • Molecular oncology

    Background:

    • Genetically identical cancer cells exhibit heterogeneous responses to therapy.
    • A subpopulation of cells enters a temporary treatment-tolerant state before tumor repopulation.
    • Understanding heterogeneity in cell cycle arrest protein p21 is crucial for cancer therapy.

    Purpose of the Study:

    • To investigate the origins of heterogeneity in p21 expression.
    • To elucidate the regulatory dynamics of p21 and its relationship with p53.
    • To explore the role of p21 regulation in treatment tolerance.

    Main Methods:

    • Live cell fluorescence microscopy to image p21 and p53 dynamics in single cells.
    • Theoretical and experimental modeling to determine p21 transcriptional regulation.
    • Analysis of p21 transcription rate dependence on p53 levels and changes.

    Main Results:

    • p21 transcription rate is dependent on the change in p53, not its absolute level.
    • An incoherent feedforward loop mediated by MDM2 governs p21 transcription.
    • This network architecture promotes rapid p21 induction and transcriptional variability.
    • Disrupting the feedforward loop leads to a quiescent state resembling treatment-tolerant persisters.

    Conclusions:

    • The p53-MDM2 incoherent feedforward loop drives p21 heterogeneity and influences treatment tolerance.
    • Targeting this regulatory loop may offer new therapeutic strategies.
    • Findings impact the development of therapies aimed at p53 activation in cancer treatment.

    More Related Videos

    Studying Cell Cycle-regulated Gene Expression by Two Complementary Cell Synchronization Protocols12:02

    Studying Cell Cycle-regulated Gene Expression by Two Complementary Cell Synchronization Protocols

    Published on: June 6, 2017

    27.3K
    Cell Death Associated with Abnormal Mitosis Observed by Confocal Imaging in Live Cancer Cells15:53

    Cell Death Associated with Abnormal Mitosis Observed by Confocal Imaging in Live Cancer Cells

    Published on: August 21, 2013

    14.9K

    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...
    4.5K
    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...
    6.3K
    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.
    35.3K
    DNA Damage can Stall the Cell Cycle02:37

    DNA Damage can Stall the Cell Cycle

    In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
    9.1K
    Inhibition of Cdk Activity02:34

    Inhibition of Cdk Activity

    The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
    4.7K
    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...
    3.8K