RBBP4

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Protein-coding gene in the species Homo sapiens

title: "RBBP4" type: doc version: 1 created: 2026-02-28 author: "Wikipedia contributors" status: active scope: public description: "Protein-coding gene in the species Homo sapiens" topic_path: "uncategorized" source: "https://en.wikipedia.org/wiki/RBBP4" license: "CC BY-SA 4.0" wikipedia_page_id: 0 wikipedia_revision_id: 0

::summary Protein-coding gene in the species Homo sapiens ::

Histone-binding protein RBBP4 (also known as RbAp48, or NURF55) is a protein that in humans is encoded by the RBBP4 gene.

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 in the brain 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:

References

References

  1. (September 1993). "A retinoblastoma-binding protein related to a negative regulator of Ras in yeast". Nature.
  2. (November 2003). "Isolation of human NURF: a regulator of Engrailed gene expression". EMBO J.
  3. "Entrez Gene: RBBP4 retinoblastoma-binding protein 4".
  4. (August 2013). "Molecular Mechanism for Age-Related Memory Loss: The Histone-Binding Protein RbAp48". Sci Transl Med.
  5. (April 1999). "Age-related defects in spatial memory are correlated with defects in the late phase of hippocampal long-term potentiation in vitro and are attenuated by drugs that enhance the cAMP signaling pathway". Proc. Natl. Acad. Sci. U.S.A..
  6. (1999). "BRCA1 interacts with components of the histone deacetylase complex". Proc. Natl. Acad. Sci. U.S.A..
  7. (2000). "Histone binding protein RbAp48 interacts with a complex of CREB binding protein and phosphorylated CREB". Mol. Cell. Biol..
  8. (2002). "Identification and functional characterization of the p66/p68 components of the MeCP1 complex". Mol. Cell. Biol..
  9. (2003). "Dual mechanisms of regulation of transcription of luteinizing hormone receptor gene by nuclear orphan receptors and histone deacetylase complexes". J. Steroid Biochem. Mol. Biol..
  10. (2003). "The metastasis-associated proteins 1 and 2 form distinct protein complexes with histone deacetylase activity". J. Biol. Chem..
  11. (2001). "The histone deacetylase HDAC3 targets RbAp48 to the retinoblastoma protein". Nucleic Acids Res..
  12. (1999). "Three proteins define a class of human histone deacetylases related to yeast Hda1p". Proc. Natl. Acad. Sci. U.S.A..
  13. (2001). "CoREST is an integral component of the CoREST- human histone deacetylase complex". Proc. Natl. Acad. Sci. U.S.A..
  14. (1997). "Histone deacetylase activity is required for full transcriptional repression by mSin3A". Cell.
  15. (1999). "MBD2 is a transcriptional repressor belonging to the MeCP1 histone deacetylase complex". Nat. Genet..
  16. (1999). "Analysis of the NuRD subunits reveals a histone deacetylase core complex and a connection with DNA methylation". Genes Dev..
  17. (2002). "Silencing of transcription of the human luteinizing hormone receptor gene by histone deacetylase-mSin3A complex". J. Biol. Chem..
  18. (1998). "A role for histone deacetylase activity in HDAC1-mediated transcriptional repression". Proc. Natl. Acad. Sci. U.S.A..
  19. (1997). "Histone deacetylases and SAP18, a novel polypeptide, are components of a human Sin3 complex". Cell.
  20. (2003). "A candidate X-linked mental retardation gene is a component of a new family of histone deacetylase-containing complexes". J. Biol. Chem..
  21. (1998). "Chromatin deacetylation by an ATP-dependent nucleosome remodelling complex". Nature.
  22. (1995). "Dual retinoblastoma-binding proteins with properties related to a negative regulator of ras in yeast". J. Biol. Chem..
  23. (2000). "RbAp48 belongs to the histone deacetylase complex that associates with the retinoblastoma protein". J. Biol. Chem..
  24. (2002). "Role of the Sin3-histone deacetylase complex in growth regulation by the candidate tumor suppressor p33(ING1)". Mol. Cell. Biol..
  25. (1998). "SAP30, a novel protein conserved between human and yeast, is a component of a histone deacetylase complex". Mol. Cell.

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