The pyruvate dehydrogenase complex in concert with the DNA/RNA-binding protein YBX1 regulates cell senescence and tumorigenesis

The activation of oncogenes is often accompanied by metabolic adaptations. The DNA/RNA-binding protein, Y-box binding protein 1 (YBX1), a well-known oncogene, is hyperactivated in nearly all cancer types. However, the metabolic hallmarks associated with YBX1 and the underlying mechanisms remain poorly understood. Here, we demonstrate that YBX1 sustains the activity of the pyruvate dehydrogenase (PDH) complex by regulating its catalytic alpha subunit, PDHA1. Mechanistically, YBX1 downregulates the expression of PDH kinases 1 and 4, leading to enhanced PDHA1 activity. Consequently, YBX1 deficiency results in significant impairment of pyruvate oxidation. Moreover, we found that YBX1, in conjunction with PDH activation, promotes epithelial cell senescence and suppresses cancer cell proliferation. These findings indicate that PDH activation imposes a constraint on the tumorigenic potential of YBX1.

Authors

Institutions

Publication Details

Journal
Journal of Biological Chemistry
Published
2025-08-12
DOI
https://doi.org/10.1016/j.jbc.2025.110585
Primary Topic
RNA modifications and cancer
Type
article
Field-Weighted Citation Impact
0.00

Funders

Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

The pyruvate dehydrogenase complex in concert with the DNA/RNA-binding protein YBX1 regulates cell senescence and tumorigenesis

Hai-long Piao, Di Chen, Yi Zhang, Jing Shi et al.
Journal of Biological Chemistry
RNA modifications and cancer
article

The pyruvate dehydrogenase complex in concert with the DNA/RNA-binding protein YBX1 regulates cell senescence and tumorigenesis

Hai-long Piao, Di Chen, Yi Zhang, Jing Shi, Qiuping Wang, Xiang Shi, Kunming Liang, Jing Lv, Yegang Ma, Tian Xia, Hong-Xu Liu, Shaojun Pei, Huan Chen
article en

Abstract

The activation of oncogenes is often accompanied by metabolic adaptations. The DNA/RNA-binding protein, Y-box binding protein 1 (YBX1), a well-known oncogene, is hyperactivated in nearly all cancer types. However, the metabolic hallmarks associated with YBX1 and the underlying mechanisms remain poorly understood. Here, we demonstrate that YBX1 sustains the activity of the pyruvate dehydrogenase (PDH) complex by regulating its catalytic alpha subunit, PDHA1. Mechanistically, YBX1 downregulates the expression of PDH kinases 1 and 4, leading to enhanced PDHA1 activity. Consequently, YBX1 deficiency results in significant impairment of pyruvate oxidation. Moreover, we found that YBX1, in conjunction with PDH activation, promotes epithelial cell senescence and suppresses cancer cell proliferation. These findings indicate that PDH activation imposes a constraint on the tumorigenic potential of YBX1.

Journal of Biological ChemistryVol. 301(9)
Dalian Institute of Chemical Physics (CN), Dalian University of Technology (CN), Liaoning Cancer Hospital & Institute (CN), China Medical University (CN)
National Natural Science Foundation of China, National Science and Technology Major Project, Liaoning Revitalization Talents Program
Openalex Percentile: Top 82%
RNA modifications and cancer
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.