Regulation of HNRNP Family by Post-translational Modifications in Cancer

Overview

Journal Cell Death Discov

Date 2024 Oct 4

PMID 39366930

Authors

Bohao Li

Mingxin Wen

Fei Gao

Yunshan Wang

Guangwei Wei

Yangmiao Duan

Affiliations

Soon will be listed here.

Abstract

Heterogeneous nuclear ribonucleoproteins (HNRNPs) represent a large family of RNA-binding proteins consisting of more than 20 members and have attracted great attention with their distinctive roles in cancer progression by regulating RNA splicing, transcription, and translation. Nevertheless, the cancer-specific modulation of HNRNPs has not been fully elucidated. The research of LC-MS/MS technology has documented that HNRNPs were widely and significantly targeted by different post-translational modifications (PTMs), which have emerged as core regulators in shaping protein functions and are involved in multiple physiological processes. Accumulating studies have highlighted that several PTMs are involved in the mechanisms of HNRNPs regulation in cancer and may be suitable therapeutic targets. In this review, we summarize the existing evidence describing how PTMs modulate HNRNPs functions on gene regulation and the involvement of their dysregulation in cancer, which will help shed insights on their clinical impacts as well as possible therapeutic tools targeting PTMs on HNRNPs.

Citing Articles

Alternative Splicing at the Crossroad of Inflammatory Bowel Diseases and Colitis-Associated Colon Cancer.

Matos P, Jordan P Cancers (Basel). 2025; 17(2).

PMID: 39858001 PMC: 11764256. DOI: 10.3390/cancers17020219.

References

Britton S, Froment C, Frit P, Monsarrat B, Salles B, Calsou P . Cell nonhomologous end joining capacity controls SAF-A phosphorylation by DNA-PK in response to DNA double-strand breaks inducers. Cell Cycle. 2009; 8(22):3717-22. DOI: 10.4161/cc.8.22.10025. View

Liu P, Cheng H, Roberts T, Zhao J . Targeting the phosphoinositide 3-kinase pathway in cancer. Nat Rev Drug Discov. 2009; 8(8):627-44. PMC: 3142564. DOI: 10.1038/nrd2926. View

Beyer A, Christensen M, Walker B, Lestourgeon W . Identification and characterization of the packaging proteins of core 40S hnRNP particles. Cell. 1977; 11(1):127-38. DOI: 10.1016/0092-8674(77)90323-3. View

Antonello Z, Hsu N, Bhasin M, Roti G, Joshi M, Van Hummelen P . Vemurafenib-resistance via de novo RBM genes mutations and chromosome 5 aberrations is overcome by combined therapy with palbociclib in thyroid carcinoma with BRAF. Oncotarget. 2017; 8(49):84743-84760. PMC: 5689570. DOI: 10.18632/oncotarget.21262. View

Diao X, Guo C, Zheng H, Zhao K, Luo Y, An M . SUMOylation-triggered ALIX activation modulates extracellular vesicles circTLCD4-RWDD3 to promote lymphatic metastasis of non-small cell lung cancer. Signal Transduct Target Ther. 2023; 8(1):426. PMC: 10625632. DOI: 10.1038/s41392-023-01685-0. View

Cansizoglu A, Lee B, Zhang Z, Fontoura B, Chook Y . Structure-based design of a pathway-specific nuclear import inhibitor. Nat Struct Mol Biol. 2007; 14(5):452-4. PMC: 3437620. DOI: 10.1038/nsmb1229. View

Briese M, Saal-Bauernschubert L, Ji C, Moradi M, Ghanawi H, Uhl M . hnRNP R and its main interactor, the noncoding RNA 7SK, coregulate the axonal transcriptome of motoneurons. Proc Natl Acad Sci U S A. 2018; 115(12):E2859-E2868. PMC: 5866599. DOI: 10.1073/pnas.1721670115. View

Li M, Ragupathi A, Patel N, Hernandez T, Magsino J, Werlen G . The RNA-binding protein AUF1 facilitates Akt phosphorylation at the membrane. J Biol Chem. 2022; 298(10):102437. PMC: 9513781. DOI: 10.1016/j.jbc.2022.102437. View

Keppetipola N, Sharma S, Li Q, Black D . Neuronal regulation of pre-mRNA splicing by polypyrimidine tract binding proteins, PTBP1 and PTBP2. Crit Rev Biochem Mol Biol. 2012; 47(4):360-78. PMC: 3422667. DOI: 10.3109/10409238.2012.691456. View

10.

Zhong Q, Xiao X, Qiu Y, Xu Z, Chen C, Chong B . Protein posttranslational modifications in health and diseases: Functions, regulatory mechanisms, and therapeutic implications. MedComm (2020). 2023; 4(3):e261. PMC: 10152985. DOI: 10.1002/mco2.261. View

11.

Wang T, Lu Z, Han T, Wang Y, Gan M, Wang J . Deacetylation of Glutaminase by HDAC4 contributes to Lung Cancer Tumorigenesis. Int J Biol Sci. 2022; 18(11):4452-4465. PMC: 9295053. DOI: 10.7150/ijbs.69882. View

12.

Grishin N . KH domain: one motif, two folds. Nucleic Acids Res. 2001; 29(3):638-43. PMC: 30387. DOI: 10.1093/nar/29.3.638. View

13.

Pinol-Roma S, Choi Y, Matunis M, Dreyfuss G . Immunopurification of heterogeneous nuclear ribonucleoprotein particles reveals an assortment of RNA-binding proteins. Genes Dev. 1988; 2(2):215-27. DOI: 10.1101/gad.2.2.215. View

14.

Wang H, Vardy L, Tan C, Loo J, Guo K, Li J . PCBP1 suppresses the translation of metastasis-associated PRL-3 phosphatase. Cancer Cell. 2010; 18(1):52-62. DOI: 10.1016/j.ccr.2010.04.028. View

15.

Vu N, Park M, Shultz J, Goehe R, Hoeferlin L, Shultz M . hnRNP U enhances caspase-9 splicing and is modulated by AKT-dependent phosphorylation of hnRNP L. J Biol Chem. 2013; 288(12):8575-8584. PMC: 3605676. DOI: 10.1074/jbc.M112.443333. View

16.

Cai K, Chen S, Zhu C, Li L, Yu C, He Z . FOXD1 facilitates pancreatic cancer cell proliferation, invasion, and metastasis by regulating GLUT1-mediated aerobic glycolysis. Cell Death Dis. 2022; 13(9):765. PMC: 9440910. DOI: 10.1038/s41419-022-05213-w. View

17.

Malumbres M, Barbacid M . Cell cycle, CDKs and cancer: a changing paradigm. Nat Rev Cancer. 2009; 9(3):153-66. DOI: 10.1038/nrc2602. View

18.

Peng C, Yang P, Zhang D, Jin C, Peng W, Wang T . KHK-A promotes fructose-dependent colorectal cancer liver metastasis by facilitating the phosphorylation and translocation of PKM2. Acta Pharm Sin B. 2024; 14(7):2959-2976. PMC: 11252482. DOI: 10.1016/j.apsb.2024.04.024. View

19.

Kedzierska H, Piekielko-Witkowska A . Splicing factors of SR and hnRNP families as regulators of apoptosis in cancer. Cancer Lett. 2017; 396:53-65. DOI: 10.1016/j.canlet.2017.03.013. View

20.

Hubbard S, Till J . Protein tyrosine kinase structure and function. Annu Rev Biochem. 2000; 69:373-98. DOI: 10.1146/annurev.biochem.69.1.373. View