Posttranslational Modifications of Smurfs: Emerging Regulation in Cancer

Overview

Journal Front Oncol

Specialty Oncology

Date 2021 Mar 15

PMID 33718111

Citations 5

Authors

Longtao Yang

Wenwen Zhou

Hui Lin

Affiliations

Soon will be listed here.

Abstract

Smad ubiquitination regulatory factors (Smurfs) belong to the Nedd4 subfamily of HECT-type E3 ubiquitin ligases. Under normal situations, Smurfs are exactly managed by upstream regulators, and thereby strictly control tumor biological processes, including cell growth, differentiation, apoptosis, polarization, epithelial mesenchymal transition (EMT), and invasion. Disruption of Smurf activity has been implicated in cancer progression, and Smurf activity is controlled by a series of posttranslational modifications (PTMs), including phosphorylation, ubiquitination, neddylation, sumoylation, and methylation. The effect and function of Smurfs depend on PTMs and regulate biological processes. Specifically, these modifications regulate the functional expression of Smurfs by affecting protein degradation and protein interactions. In this review, we summarize the complexity and diversity of Smurf PTMs from biochemical and biological perspectives and highlight the understanding of their roles in cancer.

Citing Articles

Targeting the SMURF2-HIF1α axis: a new frontier in cancer therapy.

Youssef E, Zhao S, Purcell C, Olson G, El-Deiry W Front Oncol. 2024; 14:1484515.

PMID: 39697237 PMC: 11652374. DOI: 10.3389/fonc.2024.1484515.

Post-translational modifications: The potential ways for killing cancer stem cells.

Han X, Qin H, Lu Y, Chen H, Yuan Z, Zhang Y Heliyon. 2024; 10(14):e34015.

PMID: 39092260 PMC: 11292267. DOI: 10.1016/j.heliyon.2024.e34015.

PTMs of PD-1/PD-L1 and PROTACs application for improving cancer immunotherapy.

Ren X, Wang L, Liu L, Liu J Front Immunol. 2024; 15:1392546.

PMID: 38638430 PMC: 11024247. DOI: 10.3389/fimmu.2024.1392546.

Enhanced Expression of ARK5 in Hepatic Stellate Cell and Hepatocyte Synergistically Promote Liver Fibrosis.

You Y, Gao C, Wu J, Qu H, Xiao Y, Kang Z Int J Mol Sci. 2022; 23(21).

PMID: 36361872 PMC: 9655442. DOI: 10.3390/ijms232113084.

Wei N, Chao-Yang G, Wen-Ming Z, Ze-Yuan L, Yong-Qiang S, Shun-Bai Z Front Pharmacol. 2022; 13:904448.

PMID: 36060009 PMC: 9428517. DOI: 10.3389/fphar.2022.904448.

References

Liu J, Chen Y, Huang Q, Liu W, Ji X, Hu F . IRAK2 counterbalances oncogenic Smurf1 in colon cancer cells by dictating ER stress. Cell Signal. 2018; 48:69-80. DOI: 10.1016/j.cellsig.2018.05.001. View

Choo Y, Zhang Z . Detection of protein ubiquitination. J Vis Exp. 2009; (30). PMC: 3149903. DOI: 10.3791/1293. View

Fu L, Cui C, Zhang X, Zhang L . The functions and regulation of Smurfs in cancers. Semin Cancer Biol. 2020; 67(Pt 2):102-116. DOI: 10.1016/j.semcancer.2019.12.023. View

Cao Y, Zhang L . A Smurf1 tale: function and regulation of an ubiquitin ligase in multiple cellular networks. Cell Mol Life Sci. 2012; 70(13):2305-17. PMC: 11113965. DOI: 10.1007/s00018-012-1170-7. View

Lau A, Fukushima H, Wei W . The Fbw7 and betaTRCP E3 ubiquitin ligases and their roles in tumorigenesis. Front Biosci (Landmark Ed). 2012; 17(6):2197-212. PMC: 3374336. DOI: 10.2741/4045. View

Loftus S, Liu G, Carr S, Munro S, La Thangue N . NEDDylation regulates E2F-1-dependent transcription. EMBO Rep. 2012; 13(9):811-8. PMC: 3432805. DOI: 10.1038/embor.2012.113. View

Nie J, Wu M, Wang J, Xing G, He F, Zhang L . REGgamma proteasome mediates degradation of the ubiquitin ligase Smurf1. FEBS Lett. 2010; 584(14):3021-7. DOI: 10.1016/j.febslet.2010.05.034. View

Nie J, Liu L, Xing G, Zhang M, Wei R, Guo M . CKIP-1 acts as a colonic tumor suppressor by repressing oncogenic Smurf1 synthesis and promoting Smurf1 autodegradation. Oncogene. 2016; 35(6):800. DOI: 10.1038/onc.2015.28. View

Tang L, Yamashita M, Coussens N, Tang Y, Wang X, Li C . Ablation of Smurf2 reveals an inhibition in TGF-β signalling through multiple mono-ubiquitination of Smad3. EMBO J. 2011; 30(23):4777-89. PMC: 3243605. DOI: 10.1038/emboj.2011.393. View

10.

Hua F, Mu R, Liu J, Xue J, Wang Z, Lin H . TRB3 interacts with SMAD3 promoting tumor cell migration and invasion. J Cell Sci. 2011; 124(Pt 19):3235-46. DOI: 10.1242/jcs.082875. View

11.

Geiss-Friedlander R, Melchior F . Concepts in sumoylation: a decade on. Nat Rev Mol Cell Biol. 2007; 8(12):947-56. DOI: 10.1038/nrm2293. View

12.

Lu K, Yin X, Weng T, Xi S, Li L, Xing G . Targeting WW domains linker of HECT-type ubiquitin ligase Smurf1 for activation by CKIP-1. Nat Cell Biol. 2008; 10(8):994-1002. DOI: 10.1038/ncb1760. View

13.

Johnson E . Protein modification by SUMO. Annu Rev Biochem. 2004; 73:355-82. DOI: 10.1146/annurev.biochem.73.011303.074118. View

14.

Li H, Cui Y, Wei J, Liu C, Chen Y, Cui C . VCP/p97 increases BMP signaling by accelerating ubiquitin ligase Smurf1 degradation. FASEB J. 2018; 33(2):2928-2943. DOI: 10.1096/fj.201801173R. View

15.

Sethi G, Shanmugam M, Arfuso F, Kumar A . Role of RNF20 in cancer development and progression - a comprehensive review. Biosci Rep. 2018; 38(4). PMC: 6043722. DOI: 10.1042/BSR20171287. View

16.

Chandhoke A, Chanda A, Karve K, Deng L, Bonni S . The PIAS3-Smurf2 sumoylation pathway suppresses breast cancer organoid invasiveness. Oncotarget. 2017; 8(13):21001-21014. PMC: 5400561. DOI: 10.18632/oncotarget.15471. View

17.

Enchev R, Schulman B, Peter M . Protein neddylation: beyond cullin-RING ligases. Nat Rev Mol Cell Biol. 2014; 16(1):30-44. PMC: 5131867. DOI: 10.1038/nrm3919. View

18.

Bai Y, Ying Y . The Post-translational Modifications of Smurf2 in TGF-β Signaling. Front Mol Biosci. 2020; 7:128. PMC: 7358609. DOI: 10.3389/fmolb.2020.00128. View

19.

Nie J, Xie P, Liu L, Xing G, Chang Z, Yin Y . Smad ubiquitylation regulatory factor 1/2 (Smurf1/2) promotes p53 degradation by stabilizing the E3 ligase MDM2. J Biol Chem. 2010; 285(30):22818-30. PMC: 2906273. DOI: 10.1074/jbc.M110.126920. View

20.

Xie Y, Avello M, Schirle M, McWhinnie E, Feng Y, Bric-Furlong E . Deubiquitinase FAM/USP9X interacts with the E3 ubiquitin ligase SMURF1 protein and protects it from ligase activity-dependent self-degradation. J Biol Chem. 2012; 288(5):2976-85. PMC: 3561522. DOI: 10.1074/jbc.M112.430066. View