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Regulation of PEST-containing nuclear proteins in cancer cells: implications for cancer biology and therapy

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机构: [1]Department of Traditional Chinese Medicine, Shu-Qing Medical College of Zhengzhou, Zhengzhou, Henan, China. [2]School of Stomatology, Henan University, Kaifeng, Henan, China. [3]Kaifeng Municipal Key Laboratory for Infection and Biosafety, Henan International Joint Laboratory of Nuclear Protein Regulation, School of Basic Medical Sciences, Henan University College of Medicine, Kaifeng, Henan, China. [4]Department of Urology, Institute of Urology, Sichuan University, Chengdu, China. [5]State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases and Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi, China. [6]Department of Oncology, Huaxian County Hospital, Anyang, Henan, China. [7]Faculty of Basic Medical Subjects, Shu-Qing Medical College of Zhengzhou, Zhengzhou, Henan, China. [8]The Affiliated Cancer Hospital, Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China.
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关键词: PCNP PEST motif ubiquitination proteasome cancer

摘要:
The PEST-containing nuclear protein (PCNP) is a nuclear protein involved in the regulation of cell cycle progression, protein degradation, and tumorigenesis. PCNP contains a PEST sequence, a polypeptide structural motif rich in proline (P), glutamic acid (E), serine (S), and threonine (T), which serves as a proteolytic recognition signal. The degradation of specific proteins via the PEST sequence plays a crucial role in modulating signaling pathways that control cell growth, differentiation, apoptosis, and stress responses. PCNP is primarily degraded through the ubiquitin-proteasome system (UPS) and the calpain pathway, with phosphorylation of threonine and serine residues further accelerating its degradation. The ubiquitination of PCNP by the ring finger protein NIRF in an E3 ligase-dependent manner is well documented, along with its involvement in the MAPK and PI3K/AKT/mTOR signaling pathways. Additionally, PCNP is implicated in p53-mediated cell cycle arrest and apoptosis, which are essential for inhibiting tumor growth. To explore the role of PCNP in cancer, this review examines its effects on cell growth, differentiation, proliferation, and apoptosis in lung adenocarcinoma, thyroid cancer, ovarian cancer, and other malignancies derived from glandular epithelial cells. By focusing on PCNP and its regulatory mechanisms, this study provides a scientific basis for further research on the biological functions of the PEST sequence in tumor development and cancer progression.Copyright © 2025 Jiang, Zhu, Jiang, Liu, Hussain, Luo, Sun, Ji and Li.

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出版当年[2025]版:
大类 | 3 区 医学
小类 | 4 区 肿瘤学
最新[2025]版:
大类 | 3 区 医学
小类 | 4 区 肿瘤学
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第一作者机构: [1]Department of Traditional Chinese Medicine, Shu-Qing Medical College of Zhengzhou, Zhengzhou, Henan, China.
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通讯机构: [3]Kaifeng Municipal Key Laboratory for Infection and Biosafety, Henan International Joint Laboratory of Nuclear Protein Regulation, School of Basic Medical Sciences, Henan University College of Medicine, Kaifeng, Henan, China. [6]Department of Oncology, Huaxian County Hospital, Anyang, Henan, China. [7]Faculty of Basic Medical Subjects, Shu-Qing Medical College of Zhengzhou, Zhengzhou, Henan, China.
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