PIM1 Promotes Hepatic Conversion by Suppressing Reprogramming-Induced Ferroptosis and Cell Cycle Arrest

Authors

Yangyang Yuan
Chenwei Wang
Xuran Zhuang
Shaofeng Lin
Miaomiao Luo
Wankun Deng
Jiaqi Zhou
Lihui Liu
Lina Mao
Wenbo Peng
Jian Chen
Qiangsong Wang
Yilai Shu
Yu Xue
Pengyu Huang

Publication Date

9-6-2022

Journal

Nature Communications

Abstract

Protein kinase-mediated phosphorylation plays a critical role in many biological processes. However, the identification of key regulatory kinases is still a great challenge. Here, we develop a trans-omics-based method, central kinase inference, to predict potentially key kinases by integrating quantitative transcriptomic and phosphoproteomic data. Using known kinases associated with anti-cancer drug resistance, the accuracy of our method denoted by the area under the curve is 5.2% to 29.5% higher than Kinase-Substrate Enrichment Analysis. We further use this method to analyze trans-omic data in hepatocyte maturation and hepatic reprogramming of human dermal fibroblasts, uncovering 5 kinases as regulators in the two processes. Further experiments reveal that a serine/threonine kinase, PIM1, promotes hepatic conversion and protects human dermal fibroblasts from reprogramming-induced ferroptosis and cell cycle arrest. This study not only reveals new regulatory kinases, but also provides a helpful method that might be extended to predict central kinases involved in other biological processes.

Keywords

Cell Cycle, Cell Cycle Checkpoints, Drug Resistance, Neoplasm, Ferroptosis, Humans, Phosphorylation, Protein Serine-Threonine Kinases, Proto-Oncogene Proteins c-pim-1

Comments

Supplementary Materials

PMID: 36068222