Cancer-Associated Dysregulation of Sumo Regulators: Proteases and Ligases

Abstract

SUMOylation is a post-translational modification that has emerged in recent decades as a mechanism involved in controlling diverse physiological processes and that is essential in vertebrates. The SUMO pathway is regulated by several enzymes, proteases and ligases being the main actors involved in the control of sumoylation of specific targets. Dysregulation of the expression, localization and function of these enzymes produces physiological changes that can lead to the appearance of different types of cancer, depending on the enzymes and target proteins involved. Among the most studied proteases and ligases, those of the SENP and PIAS families stand out, respectively. While the proteases involved in this pathway have specific SUMO activity, the ligases may have additional functions unrelated to sumoylation, which makes it more difficult to study their SUMO-associated role in cancer process. In this review we update the knowledge and advances in relation to the impact of dysregulation of SUMO proteases and ligases in cancer initiation and progression.

Understanding the Combined Effects of High Glucose Induced Hyper-Osmotic Stress and Oxygen Tension in the Progression of Tumourigenesis: From Mechanism to Anti-Cancer Therapeutics

“…Since histone H3 variants have significantly high coverage of disordered sequences ( Supplementary Figure S16B ), we reasoned that any aberrant post-translational modification (PTM) of the histone H3 variant could condense the protein into LLPS, which may significantly impact its nuclear trafficking, cell-cycle-associated functions and its role in cell proliferation [ 49 ]. We further speculated that acute hypoxia-induced abnormal site SUMOylation could be the type of PTM that sequesters the pH3(Ser10) in the cytoplasm via LLPS formation [ 50 ]. It could thereby explain the M-phase arrested phenotype in hypoxia.…”

“…SUMO conjugation and substrate stabilization are regulated by the sentrin-specific proteases family of proteins, which has both redundant and unique functions [ 50 ]. Acute hypoxia was found to trigger SENP1 and SENP7 isoforms, but SENP1 was identified to be pro-survival.…”

The role of SUMOylation in the neurovascular dysfunction after acquired brain injury

“…The SUMOylation pathway is regulated by several enzymes, among which proteases and ligases are the most important regulatory modes. The most studied proteases and ligases are of the SENP and PIAS families, respectively ( Lara-Urena et al, 2022 ). The proteases involved in SUMOylation modification are specific, and the most studied proteases are SENP1-3 and SENP5-7 of the SENP family ( Kunz et al, 2018 ).…”

Discovery of a Dual SENP1 and SENP2 Inhibitor

“…If SENP1 expression is incorrectly regulated, serious diseases, such as prostate [ 8 , 9 ], bladder [ 10 ], multiple myeloma [ 11 ], pancreatic [ 12 ] or neuroblastoma cancer [ 13 ] can occur. SENP1 is therefore a clinically highly relevant antitumor target and of growing interest for developing novel treatment options for cancer patients [ 14 , 15 ]. Other research showed that SENP1 deSUMOylates and stabilizes hypoxia-inducible factor 1α (HIF-1α) during hypoxia [ 16 ].…”