Related Experiment Video

Updated: Feb 10, 2026

In Vitro Analysis of E3 Ubiquitin Ligase Function
06:06

In Vitro Analysis of E3 Ubiquitin Ligase Function

Published on: May 14, 2021

6.0K

OSTM1 is a ubiquitin E3 ligase that suppresses B-cell malignancy by activating the cAMP/PKA/CREB pathway

Muhammad Usama Tariq, Namratha Sheshadri, Jianliang Shen

    Biorxiv : the Preprint Server for Biology
    |February 9, 2026
    PubMed

    Insights

    Osteoclastogenesis-associated transmembrane protein 1 (OSTM1) acts as a tumor suppressor in B-cell cancers. Loss of OSTM1 function stabilizes PDE3B, promoting cancer cell growth by disrupting the cAMP pathway.

    Area of Science:

    • Oncology
    • Molecular Biology
    • Genetics

    Background:

    • Osteoclastogenesis-associated transmembrane protein 1 (OSTM1) is crucial for lysosomal homeostasis and its mutations cause osteopetrosis.
    • OSTM1's role in cancer, particularly B-cell malignancies, was previously unexplored.

    Purpose of the Study:

    • To investigate the role of OSTM1 in B-cell malignancies.
    • To elucidate the molecular mechanisms by which OSTM1 suppresses tumors.

    Main Methods:

    • Whole-genome CRISPR/Cas9 screening in B-cell malignancies.
    • Analysis of OSTM1 expression in human B-cell cancers.
    • Ostm1 gene ablation in mice models.
    • Biochemical assays to determine OSTM1's E3 ligase activity and substrate.

    Main Results:

    • OSTM1 functions as a critical tumor suppressor in B-cell malignancies, frequently deleted or downregulated in human cancers.
    • Ostm1 deficiency in mice, alongside Cdkn2a loss, drives lymphomagenesis with high penetrance.
    • OSTM1 acts as an E3 ligase targeting phosphodiesterase 3B (PDE3B) for degradation.
    • Loss of OSTM1 leads to PDE3B stabilization, enhancing the cAMP/PKA/CREB/CREBBP tumor-promoting pathway.

    Conclusions:

    • OSTM1 is a key tumor suppressor in B-cell lymphomagenesis.
    • OSTM1 prevents B-cell cancer by regulating the cAMP pathway via PDE3B degradation.
    • OSTM1 represents a potential therapeutic target for B-cell malignancies.

    More Related Videos

    Functional Characterization of RING-Type E3 Ubiquitin Ligases In Vitro and In Planta10:27

    Functional Characterization of RING-Type E3 Ubiquitin Ligases In Vitro and In Planta

    Published on: December 5, 2019

    9.4K
    Evaluation of Substrate Ubiquitylation by E3 Ubiquitin-ligase in Mammalian Cell Lysates09:47

    Evaluation of Substrate Ubiquitylation by E3 Ubiquitin-ligase in Mammalian Cell Lysates

    Published on: May 10, 2022

    3.1K

    Related Concept Videos

    cAMP-dependent Protein Kinase Pathways01:25

    cAMP-dependent Protein Kinase Pathways

    Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
    8.6K
    Regulated Protein Degradation02:58

    Regulated Protein Degradation

    It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
    Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
    8.9K
    Intracellular Signaling Cascades01:24

    Intracellular Signaling Cascades

    Once a ligand binds to a receptor, the signal is transmitted through the membrane and into the cytoplasm. The continuation of a signal in this manner is called signal transduction. Signal transduction only occurs with cell-surface receptors, which cannot interact with most components of the cell, such as DNA. Only internal receptors can interact directly with DNA in the nucleus to initiate protein synthesis. When a ligand binds to its receptor, conformational changes occur that affect the...
    53.7K
    Factors Affecting Dissolution: Drug pKa, Lipophilicity and GI pH01:21

    Factors Affecting Dissolution: Drug pKa, Lipophilicity and GI pH

    Drug absorption within the gastrointestinal (GI) tract is a complex process influenced by several critical factors, including the site pH, the drug's dissociation constant (pKa), and the drug's lipophilicity. The GI tract exhibits a pH gradient, with an acidic environment in the stomach and a more alkaline environment in the small intestine. This pH variation directly affects the ionization state of drugs.
    A drug's pKa and the pH of the gastrointestinal (GI) tract play crucial roles...
    3.2K
    C4 Pathway and CAM01:27

    C4 Pathway and CAM

    Most plants use the C3 pathway for carbon fixation. However, some plants, such as sugar cane, corn, and cacti that grow in hot conditions, use alternative pathways to fix carbon and conserve energy loss due to photorespiration. Photorespiration is the process that occurs when the oxygen concentration is high. Under such conditions, the rubisco enzyme in the Calvin cycle binds O2 instead of CO2, which halts photosynthesis and consumes energy.
    C4 Pathway
    The C4 pathway is used by plants such as...
    49.3K
    Endocrine Signaling01:45

    Endocrine Signaling

    Endocrine cells produce hormones to communicate with remote target cells found in other organs. The hormone reaches these distant areas using the circulatory system. This exposes the whole organism to the hormone but only those cells expressing hormone receptors or target cells are affected. Thus, endocrine signaling induces slow responses from its target cells but these effects also last longer.
    68.2K