25 October 2018 : Laboratory Research
C-Terminal Binding Protein 1 Modulates Cellular Redox via Feedback Regulation of MPC1 and MPC2 in Melanoma Cells
Yu Deng12A*, Hong Li2B, Xinyi Yin3C, Hongbing Liu24B, Jing Liu5F, Dongjie Guo6F, Zheng Shi1EDOI: 10.12659/MSM.912735
Med Sci Monit 2018; 24: LBR7614-7624
Abstract
BACKGROUND: Recent studies have illustrated that the transcription co-repressor, C-terminal binding protein 1 (CtBP1), links the metabolic alterations to transcription controls in proliferation, EMT, genome stability, metabolism, and lifespan, but whether CtBP1 affects the cellular redox homeostasis is unexplored. This study was designed to investigate the mechanism of CtBP1-mediated transcription repression that contributes to the metabolic reprogramming.
MATERIAL AND METHODS: Knockdown of CtBP1 in both mouse MEF cells and human melanoma cells changed cell redox homeostasis. Further, chromatin immunoprecipitation (ChIP) and luciferase reporter assay were performed for identification of CtBP1 downstream targets, pyruvate carrier 1 and 2 genes (MPC1 and MPC2), which contribute to redox homeostasis and are transcriptionally regulated by CtBP1. Moreover, blockage of the cellular NADH level with the glycolysis inhibitor 2-Deoxy-D-Glucose (2-DG) rescued MPC1 and MPC2 expression. MTT assay and scratch assay were performed to investigate the effect of MPC1 and MPC2 expression on malignant properties of melanoma cells.
RESULTS: The data demonstrated that CtBP1 directly bound to the promoters of MPC1 and MPC2 and transcriptionally repressed them, leading to increased levels of free NADH in the cytosol and nucleus, thus positively feeding back CtBP1’s functions. Consequently, restoring MPC1 and MPC2 in human tumor cells decreases free NADH and inhibits melanoma cell proliferation and migration.
CONCLUSIONS: Our data indicate that MPC1 and MPC2 are principal mediators that link CtBP1-mediated transcription regulation to NADH production. The discovery of CtBP1 as an NADH regulator in addition to being an NADH sensor shows that CtBP1 is at the center of tumor metabolism and transcription control.
Keywords: NADH, CtBP1
Editorial
01 April 2024 : Editorial
Editorial: Forty Years of Waiting for Prevention and Cure of HIV Infection – Ongoing Challenges and Hopes for Vaccine Development and Overcoming Antiretroviral Drug ResistanceDOI: 10.12659/MSM.944600
Med Sci Monit 2024; 30:e944600
In Press
05 Mar 2024 : Clinical Research
Effects of Thermal Insulation on Recovery and Comfort of Patients Undergoing Holmium Laser LithotripsyMed Sci Monit In Press; DOI: 10.12659/MSM.942836
05 Mar 2024 : Clinical Research
Role of Critical Shoulder Angle in Degenerative Type Rotator Cuff Tears: A Turkish Cohort StudyMed Sci Monit In Press; DOI: 10.12659/MSM.943703
06 Mar 2024 : Clinical Research
Comparison of Outcomes between Single-Level and Double-Level Corpectomy in Thoracolumbar Reconstruction: A ...Med Sci Monit In Press; DOI: 10.12659/MSM.943797
21 Mar 2024 : Meta-Analysis
Economic Evaluation of COVID-19 Screening Tests and Surveillance Strategies in Low-Income, Middle-Income, a...Med Sci Monit In Press; DOI: 10.12659/MSM.943863
Most Viewed Current Articles
17 Jan 2024 : Review article
Vaccination Guidelines for Pregnant Women: Addressing COVID-19 and the Omicron VariantDOI :10.12659/MSM.942799
Med Sci Monit 2024; 30:e942799
14 Dec 2022 : Clinical Research
Prevalence and Variability of Allergen-Specific Immunoglobulin E in Patients with Elevated Tryptase LevelsDOI :10.12659/MSM.937990
Med Sci Monit 2022; 28:e937990
16 May 2023 : Clinical Research
Electrophysiological Testing for an Auditory Processing Disorder and Reading Performance in 54 School Stude...DOI :10.12659/MSM.940387
Med Sci Monit 2023; 29:e940387
01 Jan 2022 : Editorial
Editorial: Current Status of Oral Antiviral Drug Treatments for SARS-CoV-2 Infection in Non-Hospitalized Pa...DOI :10.12659/MSM.935952
Med Sci Monit 2022; 28:e935952