Related Experiment Video
Updated: Apr 30, 2026
Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs
Published on: May 15, 2019
PRMT3: new binding molecule to RhoGDI-α during mycophenolic acid-induced β-cell death
1Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, Korea; Department of Transplantation Surgery, Severance Hospital, Yonsei University Health System, Seoul, Korea.
Abstract:
Mycophenolic acid (MPA)-induced beta cell toxicity limits islet graft survival. However, the signal transduction mechanisms underlying MPA-induced β-cell toxicity have not been fully elucidated. Previously, we showed that MPA-induced pancreatic β-cell apoptosis proceeds via RhoGDI-α down-regulation linked to Rac1 activation. In the present study, we investigated factors affecting RhoGDI-α during MPA-induced β-cell apoptosis. The presence of RhoGDI-α-related protein was determined with the use of yeast 2-hybrid (Y2H) analysis. Y2H screening of RhoGDI-α was performed in yeast PBN204 strain containing 3 reporters (URA3, lacZ, and ADE2) under the control of different GAL promoters. INS-1E cells (an insulin-secreting pancreatic β-cell line) were treated with MPA for 12, 24, and 36 hours. Eighty-three real positives were obtained by Y2H analysis, and of these, arginine N-methyltransferase 3 (PRMT3) protein interacted with RhoGDI-α in INS-1E cells. PRMT3 gene expressions and its protein levels were significantly decreased during MPA-induced apoptosis. In summary, PRMT3 and RhoGDI-α were found to interact in INS-1E cells. Furthermore, MPA was found to regulate this interaction in INS-1E cells by down-regulating the gene expression of PRMT3. These findings suggest that control of the interaction between PRMT3 and RhoGDI-α could be used to prevent MPA-induced β-cell death.
Insights
Mycophenolic acid (MPA) causes beta cell death by down-regulating PRMT3, which interacts with RhoGDI-α. Targeting this PRMT3-RhoGDI-α interaction may prevent MPA-induced beta cell apoptosis.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Mycophenolic acid (MPA) toxicity impairs islet graft survival by inducing beta cell apoptosis.
- The precise molecular mechanisms of MPA-induced beta cell toxicity remain unclear.
- Previous work linked MPA-induced apoptosis to RhoGDI-α down-regulation and Rac1 activation.
Purpose of the Study:
- To investigate the factors influencing RhoGDI-α during MPA-induced beta cell apoptosis.
- To identify proteins interacting with RhoGDI-α in pancreatic beta cells.
- To elucidate the role of these interactions in MPA-induced beta cell death.
Main Methods:
- Yeast two-hybrid (Y2H) analysis was employed to screen for RhoGDI-α interacting proteins.
- INS-1E cells were treated with MPA for varying durations (12, 24, 36 hours).
- Gene expression and protein levels of interacting partners were assessed.
Main Results:
- Y2H screening identified arginine N-methyltransferase 3 (PRMT3) as a RhoGDI-α interacting protein in INS-1E cells.
- MPA treatment significantly decreased PRMT3 gene expression and protein levels.
- MPA was shown to regulate the PRMT3-RhoGDI-α interaction by down-regulating PRMT3.
Conclusions:
- PRMT3 and RhoGDI-α interact within pancreatic beta cells.
- MPA induces beta cell apoptosis, at least in part, by down-regulating PRMT3 expression and affecting its interaction with RhoGDI-α.
- Modulating the PRMT3-RhoGDI-α interaction presents a potential therapeutic strategy to prevent MPA-induced beta cell death.
More Related Videos
09:18Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
Published on: December 27, 2016
08:11Quantitative Methods to Study Protein Arginine Methyltransferase 1-9 Activity in Cells
Published on: August 7, 2021
