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CBP/p300: intramolecular and intermolecular regulations

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Frontiers in Biology

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://doi.org/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.

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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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Authors and Affiliations

  1. Department of Epigenetics and Molecular Carcinogenesis, Center for Cancer Epigenetics, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA

    Yongming Xue, Hong Wen & Xiaobing Shi

  2. Genetics and Epigenetics Graduate Program, The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, TX, 77030, USA

    Yongming Xue & Xiaobing Shi

  3. Center for Epigenetics, Van Andel Research Institute, Grand Rapids, MI, 49503, USA

    Hong Wen & Xiaobing Shi

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  1. Yongming Xue
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  2. Hong Wen
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Correspondence to Yongming Xue or Xiaobing Shi.

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Xue, Y., Wen, H. & Shi, X. CBP/p300: intramolecular and intermolecular regulations. Front. Biol. 13, 168–179 (2018). https://doi.org/10.1007/s11515-018-1502-6

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