Regulation of Corepressor Function by Nuclear NADH

By Qinghong Zhang, David W. Piston, R. Goodman. Science, 2002

617 citations recorded by the source corpus.

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 the levels required for half-maximal CtBP binding and are considerably lower than those previously reported. Agents capable of increasing NADH levels stimulate CtBP binding to its partners in vivo and potentiate CtBP-mediated repression. We propose that this ability to detect changes in nuclear NAD+/NADH ratio allows CtBP to serve as a redox sensor for transcription.

Subfields: Molecular Biology, Plant Science

View Paper: https://www.semanticscholar.org/paper/128b1e7c1d69b672a857586de14f6ac49d7af5ed

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Molecular Biology

1. Sophia Y. Lunt
2. Johan Auwerx
3. C. Cantó
4. W. Ying
5. Alisdair R. Fernie
6. M. V. Vander Heiden
7. M. Circu
8. T. Aw

In Plant Science

1. C. Cantó
2. W. Ying
3. Alisdair R. Fernie
4. Johan Auwerx
5. M. V. Vander Heiden
6. Sophia Y. Lunt
7. M. Circu
8. T. Aw

Citations in the corpus

• REACTIVE OXYGEN SPECIES, CELLULAR REDOX SYSTEMS AND APOPTOSIS (2010, positive): “For instance, NADH/NAD+ was shown to modulate gene transcription via the carboxy-terminal binding protein (CtBP) [47], Ca2+ signaling via cyclic ADP-ribose [48], cell death via poly (ADP-ribose) polymerase-1 (PARP) [49] and sirtuin protein function (see section 2.”
• Sirtuin 1 modulates cellular responses to hypoxia by deacetylating hypoxia-inducible factor 1alpha. (2010, background): “Since CtBP activity is negatively regulated by NAD (Zhang et al., 2002), we measured intracellular NAD levels during hypoxia.”
• Aerobic glycolysis: meeting the metabolic requirements of cell proliferation. (2011, positive): “Further, NADH levels regulate the transcriptional regulator C- 18 terminal binding protein, which is involved in cell growth, differentiation and transformation (Zhang et al 2002).”
• NAD+ Biosynthesis and Signaling in Plants (2018, background): “It is commonly accepted that the free NADþ passes through the nuclear pores to be used by PARP and bind to proteins such as histones like Sirtuin type deacetylase as well as transcription factors regulated by pyridine nucleotides, such as NPAS2 and CtBP (Zhang et al., 2002; Fjeld et al., 2003).”
• NAD+ metabolism and the control of energy homeostasis - a balancing act between mitochondria and the nucleus (2015, background): “Yet, the inhibition by NADH only occurs in the millimolar range, considerably above physiological NADH levels (Schmidt et al., 2004; Smith et al., 2009; Zhang et al., 2002).”
• NAD+/NADH and NADP+/NADPH in Cellular Functions and Cell Death: Regulation and Biological Consequences (2008, positive): “NADH mediates the activity of the corepressor carboxyl-terminal binding protein—-a transcriptional factor important for cell cycle regulation, development, and transformation (342); and NADH also modulates the activities of Clock:BMAL1 and NPAS2:BMAL1 that are heterodimeric transcription factors con”