UBE1C is upregulated and promotes neddylation of p53 in lung cancer

Author:

Liu Hsun1,Shih Yung‐Hsin1,Wang Wen‐Lun23ORCID,Chang Wei‐Lun4ORCID,Wang Yi‐Ching15ORCID

Affiliation:

1. Department of Pharmacology, College of Medicine National Cheng Kung University Tainan Taiwan

2. Department of Internal Medicine, E‐Da Hospital I‐Shou University Kaohsiung Taiwan

3. School of Medicine, College of Medicine I‐Shou University Kaohsiung Taiwan

4. Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine National Cheng Kung University Tainan Taiwan

5. Institute of Basic Medicine, College of Medicine National Cheng Kung University Tainan Taiwan

Abstract

AbstractNEDDylation is a type of protein post‐translational modification that has high similarity to ubiquitination. UBE1C encodes NEDDylation E1 enzyme, locates at chromatin region 3p14.1 and shows high gene dosage amplification frequency in both Asian and Caucasian lung cancer patients. However, its NEDDylation substrates and roles in tumorigenesis remain elucidated. In this study, we aim to investigate the oncogenic role of UBE1C and its involvement in how NEDDylation regulates p53 in lung cancer. We found that UBE1C mRNA overexpression and DNA amplification in most of the lung cell lines and cancer patients. Patients with UBE1C overexpression showed poor prognosis. Moreover, we demonstrated that overexpression of UBE1C and NEDD8, a NEDDylation moiety, resulted in the p53 NEDDylation with inhibition of p53 acetylation at K373 residue. Importantly, UBE1C‐mediated NEDDylation downregulated the transcriptional activity of p53 by inhibiting p53 ability to target promoter regions of its downstream transcription targets, consequently inhibiting the promoter activities and the expression of mRNA and protein of the p53 downstream genes including p21 and PTEN. In addition, UBE1C and NEDD8 overexpression promoted migration, invasion, and proliferation of lung cancer cells. Our findings suggest that UBE1C acts as an oncogene with prognostic potential and highlight a potential role of UBE1C‐mediated NEDDylation in downregulation of p53 transcriptional activity in lung cancer.

Publisher

Wiley

Subject

Genetics,Molecular Biology,Biochemistry,Biotechnology

Cited by 1 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

1. Protein neddylation and its role in health and diseases;Signal Transduction and Targeted Therapy;2024-04-05

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