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

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.

The interplay between DNA topoisomerase 2α post-translational modifications and drug resistance

“…Top2 poisons such as etoposide and doxorubicin prevent G-segment religation. Top2: type 2 DNA topoisomerase; CTD: C-terminal domain; WHD: winged helix domain; G: gated; T: transported; GHKL: Gyrase, Hsp90, Histidine Kinase, MutL domain; TOPRIM: topoisomerase-primase domain A B Aberrant PTM are often found in cancer cells and are one of their distinguishing features [11,12] . The earliest studies of PTM in Top2 proteins date back to the 1990s with the first report of a phosphorylation of purified Top2a from mouse cells [13] .…”

Melatonin disturbs SUMOylation‐mediated crosstalk between c‐Myc and nestin via MT1 activation and promotes the sensitivity of paclitaxel in brain cancer stem cells

“…Emerging evidences revealed that small ubiquitin‐like modifiers (SUMOs) such as SUMO‐1, SUMO‐2, and SUMO‐3 in mammalian systems are found covalently attached to more than 50 proteins including p53, androgen receptor, IkBα, c‐jun, histone deacetylases (HDACs), and other proteins with major functions of SUMOylation, cytoplasmic nuclear transport, transcripton, and DNA repair …”

“…32,35 Emerging evidences revealed that small ubiquitinlike modifiers (SUMOs) such as SUMO-1, SUMO-2, and SUMO-3 in mammalian systems 36 are found covalently attached to more than 50 proteins including p53, androgen receptor, IkBα, c-jun, histone deacetylases (HDACs), and other proteins 37 with major functions of SUMOylation, cytoplasmic nuclear transport, transcripton, and DNA repair. 38 Although paclitaxel, so-called taxol, has been used for chemotherapy in several cancers including ovarian cancer, breast cancer, lung cancer, Kaposi sarcoma, cervical cancer, and pancreatic cancer and cancer stem cells, 39 its resistance in stem cells 40,41 and side effects 42,43 are still hot issues for effective cancer therapy. Hence, new combination therapy with paclitaxel is attractive to overcome its resistance and side effects.…”

SUMO1 promotes the proliferation and invasion of non‐small cell lung cancer cells by regulating NF‐κB

“…Many transcriptional regulatory proteins have been shown to be substrates for the ubiquitination of this class; however, it is widely believed that a number of substrates have not been detected . SUMO1 plays an important role in tumor development; however, the molecular mechanism underlying the role of SUMO1 in cancer progression is not completely understood . SUMO1 at least partially regulates cell cycle progression through the transcriptional regulation of NF‐κB, a tumor promoter in inflammation‐associated cancers .…”