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Exploring Sequence Space to Identify Binding Sites for Regulatory RNA-Binding Proteins
Published on: August 9, 2019
Transcriptional regulation by C-terminal binding proteins
1Institute for Molecular Virology, Saint Louis University Health Sciences Center, 3681 Park Avenue, St. Louis, MO 63110, USA. chinnag@slu.edu
The International Journal of Biochemistry & Cell Biology
|March 6, 2007
Summary
C-terminal binding proteins (CtBP) are key transcriptional corepressors involved in animal development. Their activity is influenced by cellular metabolism and can involve histone modification and SUMOylation.
Area of Science:
- Molecular Biology
- Epigenetics
- Developmental Biology
Background:
- C-terminal binding proteins (CtBP) are transcriptional corepressors crucial for animal development.
- Vertebrates possess two CtBP genes (CtBP1 and CtBP2), while invertebrates have one.
- CtBP proteins share structural and functional similarities with d-isomer-specific 2-hydroxy acid dehydrogenases (D2-HDH).
Purpose of the Study:
- To elucidate the multifaceted roles of CtBP proteins in transcriptional regulation.
- To investigate the mechanisms underlying CtBP-mediated gene repression and activation.
- To explore the influence of cellular metabolic status on CtBP activity.
Main Methods:
- Analysis of CtBP protein structure and function as dimers.
- Investigation of CtBP's role in histone modification (acetylation, methylation, demethylation).
- Examination of CtBP interactions with SUMOylation machinery (UBC9, HPC2).
Main Results:
- CtBP1 complex mediates coordinated histone modifications at H3-Lysine 9 and H3-Lysine 4.
- CtBP interacts with SUMOylation enzymes, suggesting a role in SUMOylation of transcription factors.
- CtBP1 antagonizes p300/CBP coactivator activity; dCtBP and CtBP2 may activate transcription context-dependently.
- CtBP activity is modulated by the nuclear NADH/NAD+ ratio, linking it to cellular metabolism.
Conclusions:
- CtBP proteins are versatile regulators of transcription, acting as corepressors and potentially activators.
- CtBP-mediated regulation involves epigenetic modifications and SUMOylation pathways.
- Cellular metabolic state, reflected in the NADH/NAD+ ratio, significantly influences CtBP transcriptional activity.
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