X射线照射早期反应的磷酸化蛋白质组学分析揭示了可能与U251细胞辐射抗性相关的分子机制。

Phospho-Proteomics Analysis of Early Response to X-Ray Irradiation Reveals Molecular Mechanism Potentially Related to U251 Cell Radioresistance.

作者信息

Ben Diouf Ousseynou, Gilbert Antoine, Bernay Benoit, Syljuåsen Randi G, Tudor Mihaela, Temelie Mihaela, Savu Diana I, Soumboundou Mamadou, Sall Cheikh, Chevalier François

机构信息

Mixed Research Exploration and Diagnosis (UMRED), UFR-Healthy, Iba Der THIAM University of Thies, Thies BP A967, Senegal.

UMR6252 CIMAP, Team Applications in Radiobiology with Accelerated Ions, CEA-CNRS-ENSICAEN, Université de Caen Normandie, 14000 Caen, France.

出版信息

Proteomes. 2024 Dec 25;13(1):1. doi: 10.3390/proteomes13010001.

DOI:10.3390/proteomes13010001

PMID:39846632

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11755531/

Abstract

Glioblastoma (GBM) is a devastating malignant brain tumor with a poor prognosis. GBM is associated with radioresistance. Post-translational modifications (PTMs) such as protein phosphorylation can play an important role in the cellular response to radiation. To better understand the early cellular activities after radiation in GBM, we carried out a phospho-proteomic study on the U251 cell line 3 h after X-ray irradiation (6Gy) and on non-irradiated cells. Our study showed a strong modification of proteoform phosphorylation in response to radiation. We found 453 differentially expressed phosphopeptides (DEPs), with 211 being upregulated and 242 being downregulated. A GO enrichment analysis of DEPs showed a strong enrichment of the signaling pathways involved in DNA damage response after irradiation and categorized them into biological processes (BPs), cellular components (CCs) and molecular functions (MFs). Certain accessions such as BRCA1, MDC1, H2AX, MDC1, TP53BP1 were dynamically altered in our fraction and are highly associated with the signaling pathways enriched after radiation.

摘要

胶质母细胞瘤（GBM）是一种预后不良的毁灭性恶性脑肿瘤。GBM与放射抗性有关。蛋白质磷酸化等翻译后修饰（PTM）在细胞对辐射的反应中可发挥重要作用。为了更好地了解GBM辐射后早期的细胞活动，我们对X射线照射（6Gy）后3小时的U251细胞系和未照射细胞进行了磷酸化蛋白质组学研究。我们的研究表明，蛋白质磷酸化对辐射有强烈的修饰作用。我们发现了453个差异表达的磷酸肽（DEP），其中211个上调，242个下调。对DEP的基因本体（GO）富集分析表明，照射后参与DNA损伤反应的信号通路有强烈富集，并将它们分为生物过程（BP）、细胞成分（CC）和分子功能（MF）。某些蛋白如BRCA1、MDC1、H2AX、MDC1、TP53BP1在我们的样本中动态变化，并且与辐射后富集的信号通路高度相关。