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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