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核糖体蛋白 L10 的 ufmylation 修饰在胰腺腺癌发展中的作用。

The ufmylation modification of ribosomal protein L10 in the development of pancreatic adenocarcinoma.

机构信息

State Key Laboratory of Natural Medicines and Laboratory of Chemical Biology, China Pharmaceutical University, 639 Longmian Ave., Nanjing, Jiangsu Province, 211198, China.

Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & the Affiliated Cancer Hospital of Nanjing Medical University, 42 Baiziting, Kunlun Road, Nanjing, Jiangsu Province, 210009, China.

出版信息

Cell Death Dis. 2023 Jun 7;14(6):350. doi: 10.1038/s41419-023-05877-y.

DOI:10.1038/s41419-023-05877-y
PMID:37280198
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10244432/
Abstract

Pancreatic adenocarcinoma (PAAD) is the most malignant cancer with a high mortality rate. Despite the association of ribosomal protein L10 (RPL10) with PAAD and previous reports on RPL26 ufmylation, the relationship between RPL10 ufmylation and PAAD development remains unexplored. Here, we report the dissection of ufmylating process of RPL10 and potential roles of RPL10 ufmylation in PAAD development. The ufmylation of RPL10 was confirmed in both pancreatic patient tissues and cell lines, and specific modification sites were identified and verified. Phenotypically, RPL10 ufmylation significantly increased cell proliferation and stemness, which is principally resulted from higher expression of transcription factor KLF4. Moreover, the mutagenesis of ufmylation sites in RPL10 further demonstrated the connection of RPL10 ufmylation with cell proliferation and stemness. Collectively, this study reveals that PRL10 ufmylation plays an important role to enhance the stemness of pancreatic cancer cells for PAAD development.

摘要

胰腺导管腺癌（PAAD）是一种死亡率很高的恶性肿瘤。尽管核糖体蛋白 L10（RPL10）与 PAAD 有关，并且之前有报道称 RPL26 发生泛素样蛋白修饰，但 RPL10 泛素样蛋白修饰与 PAAD 发展之间的关系仍未被探索。在这里，我们报告了 RPL10 泛素化过程的剖析，以及 RPL10 泛素化在 PAAD 发展中的潜在作用。在胰腺患者组织和细胞系中均证实了 RPL10 的泛素化，并且鉴定和验证了特定的修饰位点。表型上，RPL10 泛素化显著增加了细胞增殖和干性，这主要是由于转录因子 KLF4 的表达水平升高所致。此外，RPL10 中泛素化位点的突变进一步证明了 RPL10 泛素化与细胞增殖和干性之间的联系。总之，这项研究揭示了 PRL10 泛素化在增强胰腺癌细胞干性以促进 PAAD 发展方面的重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae18/10244432/0a937d63562b/41419_2023_5877_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae18/10244432/85f4aea49c15/41419_2023_5877_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae18/10244432/4644224e796c/41419_2023_5877_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae18/10244432/fe6d6d841e69/41419_2023_5877_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae18/10244432/397438b8e471/41419_2023_5877_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae18/10244432/155e46488dc2/41419_2023_5877_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae18/10244432/0a937d63562b/41419_2023_5877_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae18/10244432/85f4aea49c15/41419_2023_5877_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae18/10244432/4644224e796c/41419_2023_5877_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae18/10244432/fe6d6d841e69/41419_2023_5877_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae18/10244432/397438b8e471/41419_2023_5877_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae18/10244432/155e46488dc2/41419_2023_5877_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae18/10244432/0a937d63562b/41419_2023_5877_Fig6_HTML.jpg

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引用本文的文献

[1]
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Sci Rep. 2025-7-11

[2]
Identification of Key Genes and Potential Therapeutic Targets in Sepsis-Associated Acute Kidney Injury Using Transformer and Machine Learning Approaches.

Bioengineering (Basel). 2025-5-16

[3]
Akt-phosphorylated UFL1 UFMylates ArpC4 to promote metastasis.

Nat Struct Mol Biol. 2025-5-26

[4]
Studies on the functional role of UFMylation in cells (Review).

Mol Med Rep. 2025-7

[5]
Microbiota-reprogrammed phosphatidylcholine inactivates cytotoxic CD8 T cells through UFMylation via exosomal SerpinB9 in multiple myeloma.

Nat Commun. 2025-3-24

[6]
Multifaceted roles of UFMylation in health and disease.

Acta Pharmacol Sin. 2025-4

[7]
UFMylation: A Potential Modification for Neurological Diseases.

Curr Neuropharmacol. 2025

[8]
Mithramycin targets head and neck cancer stem cells by inhibiting Sp1 and UFMylation.

Cancer Cell Int. 2024-12-19

[9]
Ribosomal protein S3A (RPS3A), as a transcription regulator of colony-stimulating factor 1 (CSF1), promotes glioma progression through regulating the recruitment and autophagy-mediated M2 polarization of tumor-associated macrophages.

Naunyn Schmiedebergs Arch Pharmacol. 2025-5

[10]
The emerging roles of UFMylation in the modulation of immune responses.

Clin Transl Med. 2024-9

本文引用的文献

[1]
A non-canonical scaffold-type E3 ligase complex mediates protein UFMylation.

EMBO J. 2022-11-2

[2]
Human UFSP1 is an active protease that regulates UFM1 maturation and UFMylation.

Cell Rep. 2022-8-2

[3]
Ribosomal Protein L10: From Function to Dysfunction.

Cells. 2020-11-19

[4]
Secretory Mucin 5AC Promotes Neoplastic Progression by Augmenting KLF4-Mediated Pancreatic Cancer Cell Stemness.

Cancer Res. 2021-1-1

[5]
Identification of Potential Genes for Benign Prostatic Hyperplasia and Prostate Cancer Susceptibility in Four X-chromosome Regions with High Frequency of Microvariant Alleles.

Asian Pac J Cancer Prev. 2020-8-1

[6]
UFMylation maintains tumour suppressor p53 stability by antagonizing its ubiquitination.

Nat Cell Biol. 2020-8-17

[7]
Cancer statistics, 2020.

CA Cancer J Clin. 2020-1-8

[8]
The UFMylation System in Proteostasis and Beyond.

Trends Cell Biol. 2019-11-6

[9]
UFMylation of RPL26 links translocation-associated quality control to endoplasmic reticulum protein homeostasis.

Cell Res. 2020-1

[10]
MRE11 UFMylation promotes ATM activation.

Nucleic Acids Res. 2019-5-7

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