Histone-binding protein RBBP4 (also known as RbAp48, or NURF55) 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 ''RBBP4''
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 ...
.
Function
This gene encodes a ubiquitously expressed nuclear protein that belongs to a highly conserved subfamily of
WD-repeat proteins. It is present in protein complexes involved in
histone acetylation and
chromatin assembly. It is part of the
Mi-2/NuRD complex that has been implicated in
chromatin remodeling and transcriptional repression associated with histone deacetylation. This encoded protein is also part of
corepressor complexes, which is an integral component of transcriptional silencing. It is found among several cellular proteins that bind directly to
retinoblastoma protein to regulate cell proliferation. This protein also seems to be involved in transcriptional repression of
E2F-responsive genes.
Clinical significance
A decrease of RbAp48 in the
dentate gyrus (DG) of the
hippocampus
The hippocampus (: hippocampi; via Latin from Ancient Greek, Greek , 'seahorse'), also hippocampus proper, is a major component of the brain of humans and many other vertebrates. In the human brain the hippocampus, the dentate gyrus, and the ...
in the
brain
The brain is an organ (biology), organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It consists of nervous tissue and is typically located in the head (cephalization), usually near organs for ...
is suspected to be a main cause of
memory loss in normal
aging.
An age related decrease in RbAp48 is observed in the DG from human post-mortem tissue and also in mice. Furthermore, a
gene knockin of a
dominant negative form of RbAp48 of causes memory deficits in young mice similar to that observed in older mice. Using
lentiviral gene transfer to increase the expression of RbAp48 in the brain reverses memory deficits in older mice.
RBBP4 works at least in part through the
PKA-
CREB1-
CPB pathway.
Hence one possible therapeutic approach to restore age-related memory loss is the use of PKA-CREB1-CPB pathway stimulating drugs. It has previously been shown that dopamine D1/D5 agonists such as
6-Br-APB and
SKF-38,393 that are positively coupled to
adenylyl cyclase and the
cAMP phosphodieserase inhibitor
rolipram reduce memory defects in aged mice.
Interactions
RBBP4 has been shown to
interact with:
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BRCA1,
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CREBBP,
*
GATAD2B,
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HDAC1,
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HDAC2,
[
* ]MTA2
Metastasis-associated protein MTA2 is a protein that in humans is encoded by the ''MTA2'' gene.
MTA2 is the second member of the MTA family of genes. MTA2 protein localizes in the nucleus and is a component of the nucleosome remodeling and the ...
,[
* RB,]
References
Further reading
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