Acetylation of E2F1 at K125 facilitates cell apoptosis under serum stress

E2F1 is a critical transcription factor that regulates cell cycle progression, is expressed at high levels in most cancer cells, and activates the biogenesis of proteins related to the cell cycle. Over recent years, researchers have demonstrated that E2F1 could also facilitate cellular apoptosis und...

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Main Authors: Zejun Fang, Chaoju Gong, Yanyan Hu, Tingting Cui, Min Lin, Sha Lin, Ming Ye
Format: Article
Language:English
Published: Elsevier 2025-02-01
Series:Translational Oncology
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Online Access:http://www.sciencedirect.com/science/article/pii/S1936523324003851
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author Zejun Fang
Chaoju Gong
Yanyan Hu
Tingting Cui
Min Lin
Sha Lin
Ming Ye
author_facet Zejun Fang
Chaoju Gong
Yanyan Hu
Tingting Cui
Min Lin
Sha Lin
Ming Ye
author_sort Zejun Fang
collection DOAJ
description E2F1 is a critical transcription factor that regulates cell cycle progression, is expressed at high levels in most cancer cells, and activates the biogenesis of proteins related to the cell cycle. Over recent years, researchers have demonstrated that E2F1 could also facilitate cellular apoptosis under conditions of cellular stress, thus creating a double-edged sword associated with both the regulation of cellular survival and death. However, the mechanisms responsible for these actions remain poorly understood. In this study, we demonstrated that serum stress could activate the acetylation of E2F1 at K125. Further analysis indicated that the acetylation of E2F1 at K125 could facilitate its interaction with the promoter of FAS and upregulate the levels of Fas. Furthermore, the acetylation of E2F1 attenuated its interaction with p53, thus leading to the transactivation of BAX. The upregulation of Fas and Bax activated the cleavage of caspase-3 and facilitated the apoptosis of HCC cells experiencing serum stress. Collectively, our findings indicated that the acetylation of E2F1 at K125 under serum stress leads to a functional change and a new role as an executor of cell death instead of an oncoprotein.
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series Translational Oncology
spelling doaj-art-773557b432ad4cb183214cf91812792f2025-01-22T05:41:31ZengElsevierTranslational Oncology1936-52332025-02-0152102259Acetylation of E2F1 at K125 facilitates cell apoptosis under serum stressZejun Fang0Chaoju Gong1Yanyan Hu2Tingting Cui3Min Lin4Sha Lin5Ming Ye6Central Laboratory, Sanmen People's Hospital, Sanmen 317100, China; Central Laboratory, Sanmenwan Branch, the First Affiliated Hospital, Zhejiang University School of Medicine, Sanmen 317100, China; Corresponding author at: Zejun Fang, Central Laboratory, Sanmen People's Hospital, No. 15 Taihe Road, Hairun Street, Sanmen, 317100, China.Central Laboratory, The Affiliated Xuzhou Municipal Hospital of Xuzhou Medical University, Xuzhou, 221000, ChinaDepartment of Laboratory Medicine, Sanmen People's Hospital, Sanmen, 317100, ChinaDepartment of Ultrasound, Taizhou Traditional Chinese Medicine Hospital, Jiaojiang, 318000, ChinaCentral Laboratory, Sanmen People's Hospital, Sanmen 317100, ChinaDepartment of Laboratory Medicine, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; Corresponding author at: Sha Lin, Department of Laboratory Medicine, the First Affiliated Hospital, Zhejiang University School of Medicine, No. 79 Qingchun Road, Hangzhou, 310003, China.Department of General Surgery, Sanmen People's Hospital, Sanmen 317100, China; Corresponding author at: Ming Ye, Department of General Surgery, Sanmen People's Hospital, No. 15 Taihe Road, Hairun Street, Sanmen, 317100, China.E2F1 is a critical transcription factor that regulates cell cycle progression, is expressed at high levels in most cancer cells, and activates the biogenesis of proteins related to the cell cycle. Over recent years, researchers have demonstrated that E2F1 could also facilitate cellular apoptosis under conditions of cellular stress, thus creating a double-edged sword associated with both the regulation of cellular survival and death. However, the mechanisms responsible for these actions remain poorly understood. In this study, we demonstrated that serum stress could activate the acetylation of E2F1 at K125. Further analysis indicated that the acetylation of E2F1 at K125 could facilitate its interaction with the promoter of FAS and upregulate the levels of Fas. Furthermore, the acetylation of E2F1 attenuated its interaction with p53, thus leading to the transactivation of BAX. The upregulation of Fas and Bax activated the cleavage of caspase-3 and facilitated the apoptosis of HCC cells experiencing serum stress. Collectively, our findings indicated that the acetylation of E2F1 at K125 under serum stress leads to a functional change and a new role as an executor of cell death instead of an oncoprotein.http://www.sciencedirect.com/science/article/pii/S1936523324003851Hepatocellular carcinomaE2F1HDAC5Cell apoptosisSerum stress
spellingShingle Zejun Fang
Chaoju Gong
Yanyan Hu
Tingting Cui
Min Lin
Sha Lin
Ming Ye
Acetylation of E2F1 at K125 facilitates cell apoptosis under serum stress
Translational Oncology
Hepatocellular carcinoma
E2F1
HDAC5
Cell apoptosis
Serum stress
title Acetylation of E2F1 at K125 facilitates cell apoptosis under serum stress
title_full Acetylation of E2F1 at K125 facilitates cell apoptosis under serum stress
title_fullStr Acetylation of E2F1 at K125 facilitates cell apoptosis under serum stress
title_full_unstemmed Acetylation of E2F1 at K125 facilitates cell apoptosis under serum stress
title_short Acetylation of E2F1 at K125 facilitates cell apoptosis under serum stress
title_sort acetylation of e2f1 at k125 facilitates cell apoptosis under serum stress
topic Hepatocellular carcinoma
E2F1
HDAC5
Cell apoptosis
Serum stress
url http://www.sciencedirect.com/science/article/pii/S1936523324003851
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