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Review
. 2018 Apr;52(4):1081-1094.
doi: 10.3892/ijo.2018.4280. Epub 2018 Feb 22.

The post-translational modification, SUMOylation, and cancer (Review)

Zhi-Jian Han  1 , Yan-Hu Feng  1 , Bao-Hong Gu  2 , Yu-Min Li  2 , Hao Chen  2
Affiliations
Review

The post-translational modification, SUMOylation, and cancer (Review)

Zhi-Jian Han et al. Int J Oncol. 2018 Apr.

Abstract

SUMOylation is a reversible post-translational modification which has emerged as a crucial molecular regulatory mechanism, involved in the regulation of DNA damage repair, immune responses, carcinogenesis, cell cycle progression and apoptosis. Four SUMO isoforms have been identified, which are SUMO1, SUMO2/3 and SUMO4. The small ubiquitin-like modifier (SUMO) pathway is conserved in all eukaryotes and plays pivotal roles in the regulation of gene expression, cellular signaling and the maintenance of genomic integrity. The SUMO catalytic cycle includes maturation, activation, conjugation, ligation and de-modification. The dysregulation of the SUMO system is associated with a number of diseases, particularly cancer. SUMOylation is widely involved in carcinogenesis, DNA damage response, cancer cell proliferation, metastasis and apoptosis. SUMO can be used as a potential therapeutic target for cancer. In this review, we briefly outline the basic concepts of the SUMO system and summarize the involvement of SUMO proteins in cancer cells in order to better understand the role of SUMO in human disease.

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Conflict of interest statement

Competing interests

The authors declare that they have no competing interests.

Figures

Figure 1
Figure 1
The catalytic cycle of SUMOylation. Maturation: Small ubiquitin-like modifier (SUMO) precursors are cleaved by members of the SUMO1/sentrin specific peptidase (SENP) family to expose a C-terminal di-glycine motif. Activation: The mature form of SUMO is then activated by the E1 enzyme SAE1/SAE2 which is ATP-dependent. Conjugation: The activated SUMO is then passed to the active site cysteine of the E2 conjugating enzyme, Ubc9. Ligation: SUMO is then attached to specific lysine residue in the substrate which usually requires E3 ligases. De-modification: SUMO proteins are removed from substrates by SENP, and free SUMO proteins are available for another catalytic cycle.
Figure 2
Figure 2
Association of the SUMO pathway and cancer. SUMOylation has an impact on cancer cell signaling and gene networks that regulate inflammation, immunity and DNA damage, which provides link with carcinogenesis, proliferation, metastasis and apoptosis.
Figure 3
Figure 3
The role of SUMOylation in representative cancer pathways. (a) SUMOylation in the NF-кB signaling pathway. SUMOylation and de-modification of NF-кB essential modifier (NEMO) proteins are observed both in the cytoplasm and nucleus at steps in this pathway. SUMOylation can positively or negatively regulate NF-кB activation. (b) SUMOylation in the JAK-STAT pathway. SUMOylation of STATs can inhibit phosphorylation and repress target gene expression activated by growth factors. (c) SUMOylation in the TGF-β pathway. SUMOylation exerts both promoting and suppressive effects on target gene expression through the regulation of SMADs.
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