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Acetyltransferase machinery conserved in p300/CBP-family proteins
L Wuchao Yuan1, Antonio Giordano
1Department of Physiology and Biophysics, Boston University School of Medicine, Boston, Massachusetts, MA 02118, USA.
Abstract:
CREB-binding protein (CBP) and p300 are highly conserved and functionally related transcription coactivators and histone/protein acetyltransferases. They are tumor suppressors, participate in a wide variety of physiological events, and serve as integrators among different signal transduction pathways. In this study, 11 distinct proteins that have a high degree of homology with the amino acid sequence of p300 have been identified in current protein databases. All of these 11 proteins belong to either animal or plant multicellular organisms (higher eucaryotes). Conservation of p300/CBP domains among these proteins was examined further by sequence alignment and pattern search. The domains of p300/CBP that are required for the HAT function, including PHD, putative CoA-binding, and ZZ domains, are conserved in all of these 11 proteins. This observation is consistent with the previous functional assays and indicates that they are a family of acetyltransferases, i.e. p300/CBP acetyltransferases (PCAT). TAZ domains (TAZ1 and/or TAZ2) of PCAT proteins may allow them to participate in transcription regulation by either directly recruiting transcription factors, acetylating them subsequently, or directing targeted acetylation of nucleosomal histones.
Insights
Researchers identified 11 new proteins homologous to p300, a key transcriptional coactivator. These proteins, named p300/CBP acetyltransferases (PCATs), share conserved domains essential for histone acetylation and transcription regulation.
Area of Science:
- Molecular Biology
- Biochemistry
- Genetics
Background:
- CREB-binding protein (CBP) and p300 are vital transcription coactivators and histone/protein acetyltransferases.
- These proteins are involved in numerous physiological processes and integrate diverse signaling pathways.
- CBP and p300 function as tumor suppressors.
Purpose of the Study:
- To identify and characterize proteins homologous to p300 in multicellular organisms.
- To investigate the conservation of functional domains within these homologous proteins.
- To establish a new family of proteins, p300/CBP acetyltransferases (PCATs).
Main Methods:
- Bioinformatic analysis of protein databases to identify homologous sequences.
- Sequence alignment and pattern searching to examine domain conservation.
- Comparison of identified domains with known functional domains of p300/CBP.
Main Results:
- Eleven distinct proteins with high homology to p300 were identified in higher eukaryotes.
- Key domains for HAT function (PHD, CoA-binding, ZZ) are conserved across all 11 identified proteins.
- TAZ domains were also found, suggesting roles in transcription regulation.
Conclusions:
- The identified proteins constitute a new family: p300/CBP acetyltransferases (PCATs).
- PCATs are likely involved in transcription regulation through protein acetylation or histone modification.
- The conserved domains suggest a conserved function in acetylation across species.