Regulation of Corepressor Function by Nuclear NADH

@article{Zhang2002RegulationOC,
  title={Regulation of Corepressor Function by Nuclear NADH},
  author={Qinghong Zhang and David W. Piston and Richard H. Goodman},
  journal={Science},
  year={2002},
  volume={295},
  pages={1895 - 1897}
}
The corepressor CtBP (carboxyl-terminal binding protein) is involved in transcriptional pathways important for development, cell cycle regulation, and transformation. We demonstrate that CtBP binding to cellular and viral transcriptional repressors is regulated by the nicotinamide adenine dinucleotides NAD+ and NADH, with NADH being two to three orders of magnitude more effective. Levels of free nuclear nicotinamide adenine dinucleotides, determined using two-photon microscopy, correspond to… 
CtBP as a Redox Sensor in Transcriptional Repression
TLDR
It is demonstrated that CtBP binding to transcription repressors is stimulated by NAD+ and NADH, with NADH being two to three orders of magnitude more effective, and suggest that the transcriptional corepressor CtBP may serve as a redox sensor to provide a link between gene expression and metabolism.
Transcription corepressor CtBP is an NAD(+)-regulated dehydrogenase.
NADH/NAD+ binding and linked tetrameric assembly of the oncogenic transcription factors CtBP1 and CtBP2
TLDR
Biophysical techniques are applied to address fundamental issues of CtBP assembly and nucleotide binding affinity to unambiguously demonstrate that CtBP assembles into tetramers in the presence of saturating NAD+ or NADH with tetramer to dimer dissociation constants about 100 nm.
Structural Determinants of CtBP Function
The structural characteristics of the CtBP family of transcriptional corepressors suggest an additional role for coenzyme nicotinamide adenine dinudeotide in the repression of gene expression.
Differential binding of NAD+ and NADH allows the transcriptional corepressor carboxyl-terminal binding protein to serve as a metabolic sensor
TLDR
The studies show a >100-fold higher affinity of NADH than NAD+, consistent with the proposed function of CtBP as a nuclear redox sensor, and support the possibility that changes in nuclear nicotinamide adenine dinucleotides could regulate the functions ofCtBP in cell differentiation, development, or transformation.
The CtBP2 co-repressor is regulated by NADH-dependent dimerization and possesses a novel N-terminal repression domain.
TLDR
The functional characterization of CtBP is extended by demonstrating that amino acid substitutions at Gly189 in the conserved NAD+-binding fold both abrogate the ability ofCtBP2 to homodimerize and are associated with a dramatic loss of co-repressor activity.
CtBPs promote mitotic fidelity through their activities in the cell nucleus
TLDR
It is demonstrated that it is the interaction of CtBPs with transcriptional regulators and/or chromatin-modifying enzymes in the cell nucleus, rather than their role in Golgi fission, which is critical for the maintenance of mitotic fidelity.
C-terminal binding proteins: central players in development and disease
TLDR
Although recent efforts have characterized the essential involvement of CtBPs in promoting cellular survival, the dysregulation of Ct BPs in both neurodegenerative disease and cancers remains to be fully elucidated.
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