2. Academic Validation
  3. ESF1 positively regulates MDM2 and promotes tumorigenesis

ESF1 positively regulates MDM2 and promotes tumorigenesis

  • Int J Biol Macromol. 2024 Jul 4;276(Pt 1):133652. doi: 10.1016/j.ijbiomac.2024.133652.
Pei Zhang 1,  Changning Sun 2,  Tiantian Yin 1,  Jiang Guo 3,  Daochen Chong 4,  Yanfei Tang 1,  Yunzhang Liu 1,  Yun Li 1,  Yuchao Gu 5,  Ling Lu 6
Affiliations

Affiliations

  • 1 Key Laboratory of Marine Drugs, The Ministry of Education of China, School of Medicine and Pharmacy, Ocean University of China, Qingdao, China; Laboratory for Marine Drugs and Biological Products, Laoshan Laboratory, Qingdao, China.
  • 2 Key Laboratory of Marine Drugs, The Ministry of Education of China, School of Medicine and Pharmacy, Ocean University of China, Qingdao, China; Laboratory for Marine Drugs and Biological Products, Laoshan Laboratory, Qingdao, China; College of Marine Science and Biological Engineering, Qingdao University of Science and Technology, Qingdao 266042, China.
  • 3 Department of Interventional Oncology, Beijing Ditan Hospital, Capital Medical University, Beijing, China.
  • 4 Pathology Department, Navy 971 Hospital of PLA, Qingdao, China.
  • 5 College of Marine Science and Biological Engineering, Qingdao University of Science and Technology, Qingdao 266042, China. Electronic address: guych@126.com.
  • 6 Key Laboratory of Marine Drugs, The Ministry of Education of China, School of Medicine and Pharmacy, Ocean University of China, Qingdao, China; Laboratory for Marine Drugs and Biological Products, Laoshan Laboratory, Qingdao, China. Electronic address: linglu@ouc.edu.cn.
PMID: 38971273 DOI: 10.1016/j.ijbiomac.2024.133652
Abstract

Eighteen S rRNA factor 1 (ESF1) is a predominantly nucleolar protein essential for embryogenesis. Our previous studies have suggested that Esf1 is a negative regulator of the tumor suppressor protein p53. However, it remains unclear whether ESF1 contributes to tumorigenesis. In this current research, we find that increased ESF1 expression correlates with poor survival in multiple tumors including pancreatic Cancer. ESF1 is able to regulate cell proliferation, migration, DNA damage-induced Apoptosis, and tumorigenesis. Mechanistically, ESF1 physically interacts with MDM2 and is essential for maintaining the stability of MDM2 protein by inhibiting its ubiquitination. Additionally, ESF1 also prevented stress-induced stabilization of p53 in multiple Cancer cells. Hence, our findings suggest that ESF1 is a potent regulator of the MDM2-p53 pathway and promotes tumor progression.

Keywords

ESF1; MDM2; Nucleolar protein; p53.

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