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Isolation of Primary Mouse Hepatocytes for Nascent Protein Synthesis Analysis by Non-radioactive L-azidohomoalanine Labeling Method
Published on: October 23, 2018
Tankyrase-2 regulates adipocyte differentiation through AMPK/mTOR signaling
Boglarka Rauch1, Gyula Ujlaki1,2, Szilard Poliska3
1Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, Hungary.
The FEBS Journal
|August 7, 2026
Summary
Tankyrase (TNKS) enzymes are crucial for adipocyte differentiation. Inhibiting TNKS disrupts autophagy and mTORC1, impacting cell metabolism and differentiation, suggesting potential therapeutic applications.
Area of Science:
- Cell Biology
- Metabolic Regulation
- Biochemistry
Background:
- Tankyrases (TNKSs) are enzymes initially linked to genome integrity.
- TNKSs also play roles in cellular metabolism and differentiation, including adipocytes.
- The specific function of TNKSs in adipocyte differentiation requires further elucidation.
Purpose of the Study:
- To investigate the role of TNKS1 and TNKS2 in adipocyte differentiation.
- To understand the molecular mechanisms underlying TNKS-mediated regulation of adipocyte differentiation.
- To explore the therapeutic potential of TNK inhibitors in metabolic diseases.
Main Methods:
- Gene deletion of TNKS1 or TNKS2 in adipocyte models.
- Analysis of cellular proteostasis, autophagy, AMPK, and mTORC1 activity.
- Assessment of mitochondrial oxidative phosphorylation and glycolytic flux.
- Pharmacological manipulation using autophagy activator (NV-5138) and LKB1 inhibitor (HY-10371).
- Biochemical assays to study TNKS2 interaction with LKB1.
Main Results:
- Deletion of TNKS1 or TNKS2 significantly reduced adipocyte differentiation rates.
- Loss of TNKS led to autophagy inhibition, AMPK activation, and mTORC1 suppression.
- TNKS deletion altered mitochondrial respiration and glycolytic flux, indicating increased OXPHOS coupling.
- Pharmacological activation of autophagy or inhibition of LKB1 rescued the differentiation defect in TNKS2 knockout cells.
- TNKS2 was found to ADP-ribosylate LKB1, promoting its ubiquitination and adipocyte differentiation.
Conclusions:
- TNKS enzymes are critical regulators of adipocyte differentiation.
- TNK inhibition induces adaptive metabolic changes, including altered proteostasis and energy metabolism.
- Targeting TNKS offers a potential strategy for managing metabolic diseases.
- TNK inhibition may influence tumor and immunometabolism, potentially enhancing other therapies.
Keywords:
MARUbylationautophagymetabolic adaptationmetabolic flexibilityoxidative phosphorylationtankyraseMore Related Videos
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