Nature Communications (Nov 2021)
Inhibition of histone acetyltransferase function radiosensitizes CREBBP/EP300 mutants via repression of homologous recombination, potentially targeting a gain of function
- Manish Kumar,
- David Molkentine,
- Jessica Molkentine,
- Kathleen Bridges,
- Tongxin Xie,
- Liangpeng Yang,
- Andrew Hefner,
- Meng Gao,
- Reshub Bahri,
- Annika Dhawan,
- Mitchell J. Frederick,
- Sahil Seth,
- Mohamed Abdelhakiem,
- Beth M. Beadle,
- Faye Johnson,
- Jing Wang,
- Li Shen,
- Timothy Heffernan,
- Aakash Sheth,
- Robert L. Ferris,
- Jeffrey N. Myers,
- Curtis R. Pickering,
- Heath D. Skinner
Affiliations
- Manish Kumar
- Department of Biochemistry, All India Institute of Medical Sciences (AIIMS)
- David Molkentine
- Department of Radiation Oncology, University of Pittsburgh, UPMC Hillman Cancer Center
- Jessica Molkentine
- Department of Radiation Oncology, University of Pittsburgh, UPMC Hillman Cancer Center
- Kathleen Bridges
- Department of Experimental Radiation Oncology, University of Texas, MD Anderson Cancer Center
- Tongxin Xie
- Department of Head and Neck Surgery, University of Texas, MD Anderson Cancer Center
- Liangpeng Yang
- Department of Experimental Radiation Oncology, University of Texas, MD Anderson Cancer Center
- Andrew Hefner
- Department of Radiation Oncology, University of Pittsburgh, UPMC Hillman Cancer Center
- Meng Gao
- Department of Head and Neck Surgery, University of Texas, MD Anderson Cancer Center
- Reshub Bahri
- Department of Radiation Oncology, University of Pittsburgh, UPMC Hillman Cancer Center
- Annika Dhawan
- Department of Radiation Oncology, University of Pittsburgh, UPMC Hillman Cancer Center
- Mitchell J. Frederick
- Department of Otolaryngology-Head & Neck Surgery, Baylor College of Medicine
- Sahil Seth
- TRACTION Platform, University of Texas, MD Anderson Cancer Center
- Mohamed Abdelhakiem
- Department of Radiation Oncology, University of Pittsburgh, UPMC Hillman Cancer Center
- Beth M. Beadle
- Department of Radiation Oncology, Stanford University
- Faye Johnson
- Department of Thoracic and Head and Neck Medical Oncology, University of Texas, MD Anderson Cancer Center
- Jing Wang
- The University of Texas Graduate School of Biomedical Sciences
- Li Shen
- Department of Biostatistics, University of Texas, MD Anderson Cancer Center
- Timothy Heffernan
- TRACTION Platform, University of Texas, MD Anderson Cancer Center
- Aakash Sheth
- Department of Medicine, Baylor College of Medicine
- Robert L. Ferris
- Department of Otolaryngology, University of Pittsburgh, UPMC Hillman Cancer Center
- Jeffrey N. Myers
- Department of Head and Neck Surgery, University of Texas, MD Anderson Cancer Center
- Curtis R. Pickering
- Department of Head and Neck Surgery, University of Texas, MD Anderson Cancer Center
- Heath D. Skinner
- Department of Radiation Oncology, University of Pittsburgh, UPMC Hillman Cancer Center
- DOI
- https://doi.org/10.1038/s41467-021-26570-8
- Journal volume & issue
-
Vol. 12,
no. 1
pp. 1 – 16
Abstract
Mutations in histone acetyltransferases (HATs) CREBBP and EP300 are generally thought to lead to decreased function or absence of protein product. Here the authors describe a gain of function of several CREBBP mutations leading to baseline hyper-acetylation, increased homologous recombination and potential synergy between radiation and HAT inhibition in CREBBP/EP300 mutant tumors.
