p300: expanding beyond acetylation to mastermind lactylation-dependent tumorigenesis
4 affiliations
- 1Chongqing Engineering Research Center of Antitumor Natural Drugs, Chongqing Three Gorges Medical College
- 2Chongqing Key Laboratory of Development and Utilization of Genuine Medicinal Materials in Three Gorges Reservoir Area, Chongqing Three Gorges Medical College
- 3School of Medical Technology, Chongqing Three Gorges Medical College
- 4School of Basic Medical Sciences, Chongqing Three Gorges Medical College
Abstract
The transcription coactivator p300 is canonically recognized as a histone acetyltransferase that orchestrates chromatin remodeling and gene expression. However, recent breakthroughs have expanded the catalytic landscape of p300 beyond acetylation to include lactylation, a metabolic stress induced modification driven by lactate accumulation. As a principal lactyl-transferase, p300 acts as a sensor of the Warburg effect, directly translating cellular metabolic status into epigenetic regulation. This catalytic duality extends beyond histones to non-histone substrates, profoundly impacting tumor progression, immune evasion, and metabolic adaptation. This review synthesizes the established roles of p300 in acetylation while critically examining its emerging identity as a writer of protein lactylation. By highlighting the competitive interplay between acetyl-CoA and lactyl-CoA usage, we position p300 as a central integrator that couples metabolic signaling with transcriptional reprogramming in cancer and other pathological states. Furthermore, this review bridges the gap between mechanistic discovery and clinical translation by evaluating the therapeutic potential of targeting p300 lactyl-transferase activity. We highlight the emerging clinical relevance of p300 inhibitors, such as CCS1477 (in Phase I/II trials) and the preclinical agent A-485, discussing how these compounds, originally designed for acetylation or bromodomain inhibition, may be repurposed to dismantle lactylation-driven oncogenic networks and overcome metabolic immune evasion in refractory tumors.
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BibTeX
@article{jiang2026p300,
title = {{p300: expanding beyond acetylation to mastermind lactylation-dependent tumorigenesis}},
author = {Su-Ting Jiang and Xiao He and Yue Wang and Wan-Song Chen and Peng Guan},
journal = {Frontiers in Cell and Developmental Biology},
year = {2026},
month = may,
doi = {10.3389/fcell.2026.1811421},
url = {https://doi.org/10.3389/fcell.2026.1811421},
note = {CC BY},
}
RIS
TY - JOUR
TI - p300: expanding beyond acetylation to mastermind lactylation-dependent tumorigenesis
AU - Su-Ting Jiang
AU - Xiao He
AU - Yue Wang
AU - Wan-Song Chen
AU - Peng Guan
PY - 2026
DA - 2026/05/13
JO - Frontiers in Cell and Developmental Biology
DO - 10.3389/fcell.2026.1811421
UR - https://doi.org/10.3389/fcell.2026.1811421
AB - The transcription coactivator p300 is canonically recognized as a histone acetyltransferase that orchestrates chromatin remodeling and gene expression. However, recent breakthroughs have expanded the catalytic landscape of p300 beyond acetylation to include lactylation, a metabolic stress induced modification driven by lactate accumulation. As a principal lactyl-transferase, p300 acts as a sensor of the Warburg effect, directly translating cellular metabolic status into epigenetic regulation. This catalytic duality extends beyond histones to non-histone substrates, profoundly impacting tumor progression, immune evasion, and metabolic adaptation. This review synthesizes the established roles of p300 in acetylation while critically examining its emerging identity as a writer of protein lactylation. By highlighting the competitive interplay between acetyl-CoA and lactyl-CoA usage, we position p300 as a central integrator that couples metabolic signaling with transcriptional reprogramming in cancer and other pathological states. Furthermore, this review bridges the gap between mechanistic discovery and clinical translation by evaluating the therapeutic potential of targeting p300 lactyl-transferase activity. We highlight the emerging clinical relevance of p300 inhibitors, such as CCS1477 (in Phase I/II trials) and the preclinical agent A-485, discussing how these compounds, originally designed for acetylation or bromodomain inhibition, may be repurposed to dismantle lactylation-driven oncogenic networks and overcome metabolic immune evasion in refractory tumors.
SN - 2296-634X
ER -