The role of SUMOylation in ageing and senescent decline

Princz, Andrea; Tavernarakis, Nektarios

doi:10.1016/j.mad.2017.01.002

Cited by 26 publications

(21 citation statements)

References 57 publications

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“…Insight into how SUMO modification coordinates the fundamental process of DNA double-strand break (DSB) repair is emerging. Indeed this may contribute to further understanding of the established role SUMOylation has in ageing and senescence [ 165 ], and neurological disorders [ 166 ]. The role of SUMO in transcriptional repression and maintenance of heterochromatin appears co-opted in the acute response to damage but is then overcome to open chromatin structure.…”

Section: Conclusion and Questionsmentioning

confidence: 99%

SUMO, a small, but powerful, regulator of double-strand break repair

Garvin

Morris²

2017

Phil. Trans. R. Soc. B

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The response to a DNA double-stranded break in mammalian cells is a process of sensing and signalling the lesion. It results in halting the cell cycle and local transcription and in the mediation of the DNA repair process itself. The response is launched through a series of post-translational modification signalling events coordinated by phosphorylation and ubiquitination. More recently modifications of proteins by Small Ubiquitin-like MOdifier (SUMO) isoforms have also been found to be key to coordination of the response (Morris et al. 2009 Nature 462, 886–890 (doi:10.1038/nature0859310.1038/nature08593); Galanty et al. 2009 Nature 462, 935–939 (doi:10.1038/nature0865710.1038/nature08657)). However our understanding of the role of SUMOylation is slight compared with our growing knowledge of how ubiquitin drives signal amplification and key chromatin interactions. In this review we consider our current knowledge of how SUMO isoforms, SUMO conjugation machinery, SUMO proteases and SUMO-interacting proteins contribute to directing altered chromatin states and to repair-protein kinetics at a double-stranded DNA lesion in mammalian cells. We also consider the gaps in our understanding.This article is part of the themed issue ‘Chromatin modifiers and remodellers in DNA repair and signalling’.

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Section: Conclusion and Questionsmentioning

confidence: 99%

SUMO, a small, but powerful, regulator of double-strand break repair

Garvin

Morris²

2017

Phil. Trans. R. Soc. B

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“…More and more researches have realized the importance of SUMOylation in the normal function of the body [ 4 ]. Along with the accumulating knowledge on its biological functions, SUMOylation has been reported to regulate protein subcellular localization, protein–DNA binding, protein–protein interactions, transcriptional regulation, DNA repair and genome organization [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Protein SUMOylation modification and its associations with disease

et al. 2017

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SUMOylation, as a post-translational modification, plays essential roles in various biological functions including cell growth, migration, cellular responses to stress and tumorigenesis. The imbalance of SUMOylation and deSUMOylation has been associated with the occurrence and progression of various diseases. Herein, we summarize and discuss the signal crosstalk between SUMOylation and ubiquitination of proteins, protein SUMOylation relations with several diseases, and the identification approaches for SUMOylation site. With the continuous development of bioinformatics and mass spectrometry, several accurate and high-throughput methods have been implemented to explore small ubiquitin-like modifier-modified substrates and sites, which is helpful for deciphering protein SUMOylation-mediated molecular mechanisms of disease.

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“…Recent studies have reported that SUMOylation is frequently upregulated during malignant transformation in a range of tumors, including lung cancer, prostate cancer, gastric cancer, breast cancer and glioma (20)(21)(22)(23)(24)(25)37). Ubc9, the only SUMO-E2-conjugating enzyme, is has been demonstrated to be overexpressed in various types of cancer cells (33)(34)(35)(36).…”

Section: Discussionmentioning

confidence: 99%

“…conjugating enzyme and SUMO ligase, which attach SUMO to target proteins (20)(21)(22). Ubc9, the only SUMO E2 conjugating enzyme, is often overexpressed in tumors (23)(24)(25), suggesting that it may be involved in molecular events required during cancer development (21,24,25). Recently, Kjenseth et al (26) reported that Cx43 is covalently modified and regulated by SUMOylation in HeLa cells.…”

Section: Silencing Ubc9 Expression Suppresses Osteosarcoma Tumorigenementioning

confidence: 99%

Silencing Ubc9 expression suppresses osteosarcoma tumorigenesis and enhances chemosensitivity to HSV-TK/GCV by regulating connexin�43 SUMOylation

Zhang

et al. 2018

Int J Oncol

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The ability of herpes simplex virus thymidine kinase/ganciclovir (HSV-TK/GCV) systems to kill tumor cells is partially dependent on the integrity of gap junction intercellular communication (GJIC) of targeted tumor cells. Recent studies have suggested that connexin 43 (Cx43), which serves a role in gap junction-mediated intercellular communication, is regulated by small ubiquitin-like modifiers (SUMOs). However, the roles of these post-translational modifications remain to be elucidated. The present study demonstrated overexpression of SUMO‑conjugating enzyme Ubc9 (Ubc9) protein in osteosarcoma. Silencing Ubc9 by siRNA inhibited osteosarcoma cell proliferation and migration, and significantly increased the sensitivity of cells to HSV-TK/GCV systems both in vitro and in vivo. Further experimentation demonstrated that silencing Ubc9 induced decoupling of SUMO1 from Cx43, generating increased free Cx43 levels, which is important for reconstructing GJIC and recovering cellular functions. In conclusion, the present study revealed a novel method for the effective restoration of GJIC in osteosarcoma cells, which may increase their sensitivity to conventional chemotherapy.

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The role of SUMOylation in ageing and senescent decline

Cited by 26 publications

References 57 publications

SUMO, a small, but powerful, regulator of double-strand break repair

SUMO, a small, but powerful, regulator of double-strand break repair

Protein SUMOylation modification and its associations with disease

Silencing Ubc9 expression suppresses osteosarcoma tumorigenesis and enhances chemosensitivity to HSV-TK/GCV by regulating connexin�43 SUMOylation

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