NADH/NAD binding and linked tetrameric assembly of the oncogenic transcription factors CtBP1 and CtBP2
Student Authors
Anne JecroisAcademic Program
Biochemistry and Molecular PharmacologyUMass Chan Affiliations
Biochemistry and Molecular BiotechnologyMorningside Graduate School of Biomedical Sciences
Document Type
Journal ArticlePublication Date
2022-01-17
Metadata
Show full item recordAbstract
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 nm. Isothermal titration calorimetry measurements of NAD(H) binding to CtBP show dissociation constants between 30 and 500 nm, 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.Source
Erlandsen H, Jecrois AM, Nichols JC, Cole JL, Royer WE Jr. NADH/NAD+ binding and linked tetrameric assembly of the oncogenic transcription factors CtBP1 and CtBP2. FEBS Lett. 2022 Feb;596(4):479-490. doi: 10.1002/1873-3468.14276. Epub 2022 Jan 17. PMID: 34997967.DOI
10.1002/1873-3468.14276Permanent Link to this Item
http://hdl.handle.net/20.500.14038/52067PubMed ID
34997967Rights
© 2022 Federation of European Biochemical Societies.ae974a485f413a2113503eed53cd6c53
10.1002/1873-3468.14276