C-terminal-binding protein 1 also known as CtBP1 is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
that in humans is encoded by the ''CTBP1''
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
.
CtBP1 is one of two CtBP proteins, the other protein being CtBP2.
Function
The CtBP1 protein was originally identified as a human protein that bound a PLDLS motif in the
C-terminus
The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, carboxy tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein
Proteins are large biomolecules and macromolecules that comp ...
of adenovirus E1A proteins. It and the related protein
CTBP2 were later shown to function as transcriptional
corepressor
In genetics and molecular biology, a corepressor is a molecule that represses the expression of genes. In prokaryotes
A prokaryote (; less commonly spelled procaryote) is a single-celled organism whose cell lacks a nucleus and other membra ...
s.
That is, regulatory proteins that bind to sequence-specific DNA-binding proteins and help turn genes off. CtBPs do this by recruiting histone modifying enzymes that add repressive histone marks and remove activating marks. CtBP proteins can also self-associate and presumably bring together gene regulatory complexes.
CtBP1 is broadly expressed from embryo to adult, while CtBP2 has a somewhat more restricted pattern of expression. CtBPs have multiple biological roles and appear to be most important in regulating the epithelial to mesenchymal transition, as well as influencing metabolism. They do the latter by binding NADH in preference to NAD+, thereby sensing the
NADH/NAD+ ratio. When bound, it undergoes a conformational change that allows it to dimerize and associate with its partner proteins and silence specific genes.
During skeletal and T cell development, CtBP1 and CtBP2 associate with the PLDLSL domain of δEF1, a cellular zinc finger-homeodomain protein, and thereby enhances δEF1-induced transcriptional silencing. CtBP also binds the
Kruppel-like factors family of zinc finger proteins
KLF3,
KLF8 and
KLF12. In addition, CtBP complexes with CtIP, a 125 kDa protein that recognizes distinctly different protein motifs from CtBP. CtIP binds to the BRCT repeats within the breast cancer gene BRCA1 and enables CtBP to influence BRCA1 activity. Both proteins can also interact with a polycomb group protein complex which participates in regulation of gene expression during development. Alternative splicing of transcripts from this gene results in multiple transcript variants.
C-terminal-binding protein interacting protein (CtIP) is a binding partner with CtBP, which contribute to
transcription repression and
cell cycle
The cell cycle, or cell-division cycle, is the sequential series of events that take place in a cell (biology), cell that causes it to divide into two daughter cells. These events include the growth of the cell, duplication of its DNA (DNA re ...
regulation, and which have a role in the cellular response to
DNA damage.
Interactions
CTBP1 has been shown to
interact with:
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ACTL6B,
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ARF,
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EVI1
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FOXP2
Forkhead box protein P2 (FOXP2) is a protein that, in humans, is encoded by the ''FOXP2'' gene. FOXP2 is a member of the forkhead box family of transcription factors, proteins that Regulation of gene expression, regulate gene expression by DNA- ...
,
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HDAC1,
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IKZF1,
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IKZF4,
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KLF3,
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KLF8,
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Mdm2,
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MLL,
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NRIP1,
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Pinin,
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RBBP8,
and
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TGIF1.
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GATA1
GATA-binding factor 1 or GATA-1 (also termed Erythroid transcription factor) is the founding member of the GATA family of transcription factors. This protein is widely expressed throughout vertebrate species. In humans and mice, it is encoded b ...
.
References
Further reading
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External links
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{{Transcription coregulators
Transcription coregulators