CBP/p300: intramolecular and intermolecular regulations

Abstract

BACKGROUND: CREB binding protein (CBP) and its close paralogue p300 are transcriptional coactivators with intrinsic acetyltransferase activity. Both CBP/p300 play critical roles in development and diseases. The enzymatic and biological functions of CBP/p300 are tightly regulated by themselves and by external factors. However, a comprehensive up-to-date review of the intramolecular and intermolecular regulations is lacking.

OBJECTIVE: To summarize the molecular mechanisms regulating CBP/p300s functions.

METHODS: A systematic literature search was conducted using the PubMed (https://www.ncbi.nlm.nih.gov/pubmed/) for literatures published during 1985-2018. Keywords “CBP regulation” or “p300 regulation” were used for the search.

RESULTS: The functions of CBP/p300, especially their acetyltransferase activity and chromatin association, are regulated both intramolecularly by their autoinhibitory loop (AIL), bromodomain, and PHD-RING region and intermolecularly by their interacting partners. The intramolecular mechanisms equip CBP/p300 with the capability of self-regulation while the intermolecular mechanisms allow them to respond to various cell signaling pathways.

CONCLUSION: Investigations into those regulation mechanisms are crucial to our understanding of CBP/p300s role in development and pathogenesis. Pharmacological interventions targeting these regulatory mechanisms have therapeutic potentials.

Keywords

p300 / CBP / histone acetylation / autoacetylation / HAT

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Compliance with ethics guidelines

The authors declare no conflict of interest. This manuscript is a review article and does not involve a research protocol requiring approval by the relevant institutional review board or ethics committee.

Acknowledgments

We thank members of the Shi laboratory for discussions. This work was supported in part by grants from NIH/NCI (CA204020) and Leukemia & Lymphoma Society (1339-17) to X.S.. X.S. is a Scientific Advisory Board member of EpiCypher.

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