Comparative Acetylation and Ubiquitination Profiling in Cervical Cancer-Cell Models Supports a Proposed Lysine-Fate Code
4 affiliations
- 1Centro de Ciencias Genómicas, Universidad Nacional Autónoma de México (UNAM), Cuernavaca 62210, Mexico
- 2Section for Clinical Chemistry, Department of Translational Medicine, Lund University, 22242 Lund, Sweden
- 3Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Republic of Korea
- 41st Department of Surgery, Tokyo Medical University, Tokyo 160-8582, Japan
Abstract
Post-translational modifications are rarely studied as an integrated system. Most studies have focused on acetylation or ubiquitination in isolation, despite both frequently targeting the same lysine residues on the same proteins. This study investigated whether the interplay between these modifications, rather than their individual effects, constitutes a meaningful regulatory layer in cervical cancer cells. Quantitative stoichiometric proteomics was applied to HPV-positive and HPV-negative cell models, with a non-cancerous keratinocyte cell line serving as the control. The results demonstrate that acetylation and ubiquitination form coordinated, context-dependent patterns rather than acting independently. In HPV-positive cells acetylation predominated and was enriched in transcriptional regulators. Conversely, the HPV-negative C33A line exhibited a substantially larger ubiquitinome, indicative of increased proteostatic surveillance. Site-specific stoichiometry analysis revealed that the relative occupancy of each modification at shared lysine residues determines regulatory outcomes, rather than their mere presence. This competition is proposed to constitute a “lysine-fate code” that integrates transcriptional regulation, metabolic adaptation, and immune signaling into a unified proteostatic logic. Beyond their implications for cervical cancer biology, these findings suggest that the acetylation–ubiquitination balance may represent a key regulatory principle. Targeting enzymes that modulate this balance could provide novel therapeutic strategies that surpass single-pathway inhibition.
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BibTeX
@article{bastida2026comparative,
title = {{Comparative Acetylation and Ubiquitination Profiling in Cervical Cancer-Cell Models Supports a Proposed Lysine-Fate Code}},
author = {Ramiro Alonso Bastida and Marisol Ayala Reyes and György Marko-Varga and Jeovanis Gil and Sergio Encarnación-Guevara},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27219749},
url = {https://www.mdpi.com/1422-0067/27/21/9749},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Comparative Acetylation and Ubiquitination Profiling in Cervical Cancer-Cell Models Supports a Proposed Lysine-Fate Code
AU - Ramiro Alonso Bastida
AU - Marisol Ayala Reyes
AU - György Marko-Varga
AU - Jeovanis Gil
AU - Sergio Encarnación-Guevara
PY - 2026
DA - 2026/10/30
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27219749
UR - https://www.mdpi.com/1422-0067/27/21/9749
AB - Post-translational modifications are rarely studied as an integrated system. Most studies have focused on acetylation or ubiquitination in isolation, despite both frequently targeting the same lysine residues on the same proteins. This study investigated whether the interplay between these modifications, rather than their individual effects, constitutes a meaningful regulatory layer in cervical cancer cells. Quantitative stoichiometric proteomics was applied to HPV-positive and HPV-negative cell models, with a non-cancerous keratinocyte cell line serving as the control. The results demonstrate that acetylation and ubiquitination form coordinated, context-dependent patterns rather than acting independently. In HPV-positive cells acetylation predominated and was enriched in transcriptional regulators. Conversely, the HPV-negative C33A line exhibited a substantially larger ubiquitinome, indicative of increased proteostatic surveillance. Site-specific stoichiometry analysis revealed that the relative occupancy of each modification at shared lysine residues determines regulatory outcomes, rather than their mere presence. This competition is proposed to constitute a “lysine-fate code” that integrates transcriptional regulation, metabolic adaptation, and immune signaling into a unified proteostatic logic. Beyond their implications for cervical cancer biology, these findings suggest that the acetylation–ubiquitination balance may represent a key regulatory principle. Targeting enzymes that modulate this balance could provide novel therapeutic strategies that surpass single-pathway inhibition.
SN - 1422-0067
ER -