Arginine Methylation of HnRNPK Inhibits the DDX3-hnRNPK Interaction to Play an Anti-Apoptosis Role in Osteosarcoma Cells

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2021 Sep 28

PMID 34575922

Citations 7

Authors

Chiao-Che Chen

Jen-Hao Yang

Shu-Ling Fu

Wey-Jinq Lin

Chao-Hsiung Lin

Affiliations

Soon will be listed here.

Abstract

Heterogeneous nuclear ribonucleoprotein K (hnRNPK) is an RNA/DNA binding protein involved in diverse cell processes; it is also a p53 coregulator that initiates apoptosis under DNA damage conditions. However, the upregulation of hnRNPK is correlated with cancer transformation, progression, and migration, whereas the regulatory role of hnRNPK in cancer malignancy remains unclear. We previously showed that arginine methylation of hnRNPK attenuated the apoptosis of U2OS osteosarcoma cells under DNA damage conditions, whereas the replacement of endogenous hnRNPK with a methylation-defective mutant inversely enhanced apoptosis. The present study further revealed that an RNA helicase, DDX3, whose C-terminus preferentially binds to the unmethylated hnRNPK and could promote such apoptotic enhancement. Moreover, C-terminus-truncated DDX3 induced significantly less apoptosis than full-length DDX3. Notably, we also identified a small molecule that docks at the ATP-binding site of DDX3, promotes the DDX3-hnRNPK interaction, and induces further apoptosis. Overall, we have shown that the arginine methylation of hnRNPK suppresses the apoptosis of U2OS cells via interfering with DDX3-hnRNPK interaction. On the other hand, DDX3-hnRNPK interaction with a proapoptotic role may serve as a target for promoting apoptosis in osteosarcoma cells.

Citing Articles

Dysregulation of arginine methylation in tumorigenesis.

Li X, Song Y, Mu W, Hou X, Ba T, Ji S Front Mol Biosci. 2024; 11:1420365.

PMID: 38911125 PMC: 11190088. DOI: 10.3389/fmolb.2024.1420365.

RNA helicase DDX3 regulates RAD51 localization and DNA damage repair in Ewing sarcoma.

Randolph M, Afifi M, Gorthi A, Weil R, Wilky B, Weinreb J iScience. 2024; 27(2):108925.

PMID: 38323009 PMC: 10844834. DOI: 10.1016/j.isci.2024.108925.

Heterogeneous nuclear ribonucleoprotein K promotes cap-independent translation initiation of retroviral mRNAs.

Fuentes Y, Olguin V, Lopez-Ulloa B, Mendonca D, Ramos H, Abdalla A Nucleic Acids Res. 2024; 52(5):2625-2647.

PMID: 38165048 PMC: 10954487. DOI: 10.1093/nar/gkad1221.

Comparative Shotgun Proteomics Reveals the Characteristic Protein Signature of Osteosarcoma Subtypes.

Alaa M, Al-Shehaby N, Anwar A, Farid N, Shawky M, Zamzam M Cells. 2023; 12(17).

PMID: 37681913 PMC: 10487120. DOI: 10.3390/cells12172179.

Functional Role of RBP in Osteosarcoma: Regulatory Mechanism and Clinical Therapy.

Que Z, Yang K, Wang N, Li S, Li T Anal Cell Pathol (Amst). 2023; 2023:9849719.

PMID: 37426488 PMC: 10328736. DOI: 10.1155/2023/9849719.

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