NADH/NAD+ binding and linked tetrameric assembly of the oncogenic transcription factors CtBP1 and CtBP2

2022/01/08 by Heidi Erlandsen, Anne M. Jecrois, Jeffry C. Nichols +2 · 8 citations
Biochemistry, Genetics and Molecular Biology · #Kruppel-like factors research #Microbial metabolism and enzyme function #RNA modifications and cancer

paper · pdf · doi:10.1002/1873-3468.14276

Abstract

The activation of oncogenic C‐terminal binding Protein (CtBP) transcriptional activity is coupled with NAD(H) binding and homo‐oligomeric assembly, although the level of CtBP assembly and nucleotide binding affinity continues to be debated. Here, we apply biophysical techniques to address these fundamental issues for CtBP1 and CtBP2. Our ultracentrifugation results unambiguously demonstrate that CtBP assembles into tetramers in the presence of saturating NAD + or NADH with tetramer to dimer dissociation constants about 100 n m . Isothermal titration calorimetry measurements of NAD(H) binding to CtBP show dissociation constants between 30 and 500 n m , depending on the nucleotide and paralog. Given cellular levels of NAD + , CtBP is likely to be fully saturated with NAD under physiological concentrations suggesting that CtBP is unable to act as a sensor for NADH levels.

Cited by

• The Cynosure of CtBP: Evolution of a Bilaterian Transcriptional Corepressor. [europepmc]
• Master corepressor inactivation through multivalent SLiM-induced polymerization mediated by the oncogene suppressor RAI2. [europepmc]
• C-Terminal Binding Protein: Regulator between Viral Infection and Tumorigenesis. [europepmc]
• Analytical Post-Embedding Immunogold-Electron Microscopy with Direct Gold-Labelled Monoclonal Primary Antibodies against RIBEYE A- and B-Domain Suggests a Refined Model of Synaptic Ribbon Assembly. [europepmc]
• C-terminal binding protein 2 interacts with JUNB to control macrophage inflammation. [europepmc]
• CtBP1/2 oligomerization promotes G9a-Mediated transcriptional repression. [europepmc]
• NAD(H)-dependent corepressor CTBP1 integrates metabolic signals to drive oncogenic programs. [europepmc]
• Metabolic oxidoreductases: central regulators of the epigenetic landscapes in stemness. [europepmc]

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