SUMO proteases: from cellular functions to disease

Claessens, Laura A.; Vertegaal, Alfred C.O.

doi:10.1016/j.tcb.2024.01.002

Cited by 10 publications

(1 citation statement)

References 82 publications

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“…SUMO1-3 are deconjugated by SENP proteases (SENP1-3 and 5-7) [ 6 , 7 ], USPL1 (ubiquitin specific peptidase-like 1) [ 8 , 9 ] and DeSi1/2 (DeSUMOylating isopeptidases 1/2) [ 10 ]. SENP1/2 deconjugate SUMO1.…”

Section: Introduction To Sumoylationmentioning

confidence: 99%

SUMO and the DNA damage response

Bhachoo,

Garvin

2024

Biochemical Society Transactions

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The preservation of genome integrity requires specialised DNA damage repair (DDR) signalling pathways to respond to each type of DNA damage. A key feature of DDR is the integration of numerous post-translational modification signals with DNA repair factors. These modifications influence DDR factor recruitment to damaged DNA, activity, protein-protein interactions, and ultimately eviction to enable access for subsequent repair factors or termination of DDR signalling. SUMO1-3 (small ubiquitin-like modifier 1-3) conjugation has gained much recent attention. The SUMO-modified proteome is enriched with DNA repair factors. Here we provide a snapshot of our current understanding of how SUMO signalling impacts the major DNA repair pathways in mammalian cells. We highlight repeating themes of SUMO signalling used throughout DNA repair pathways including the assembly of protein complexes, competition with ubiquitin to promote DDR factor stability and ubiquitin-dependent degradation or extraction of SUMOylated DDR factors. As SUMO ‘addiction’ in cancer cells is protective to genomic integrity, targeting components of the SUMO machinery to potentiate DNA damaging therapy or exacerbate existing DNA repair defects is a promising area of study.

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Section: Introduction To Sumoylationmentioning

confidence: 99%

SUMO and the DNA damage response

Bhachoo,

Garvin

2024

Biochemical Society Transactions

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SUMO‐specific proteases: SENPs in oxidative stress‐related signaling and diseases

Jiao,

Zhang,

Yang

2024

BioFactors

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Oxidative stress is employed to depict a series of responses detrimental to normal cellular functions resulting from an imbalance between intracellular oxidants, mainly reactive oxygen species and antioxidant defenses. Oxidative stress often contributes to the development of various diseases, including cancer, cardiovascular diseases, and neurodegenerative diseases. In this process, the relationship between small ubiquitin‐like modifier (SUMO) and oxidative stress has garnered significant attention, with its posttranslational modification (PTM) frequently serving as a marker of oxidative stress status. Sentrin/SUMO‐specific proteases (SENPs), affected by alternative splicing, PTMs such as phosphorylation and ubiquitination, and various protein interactions, are crucial molecules in the SUMO process. The human SENP family has six members (SENP1–3, SENP5–7), which are classified into two categories based on sequence similarity, substrate specificity, and subcellular location. They have two core functions in the human body: first, by cleaving the precursor SUMO and exposing the C‐terminal glycine, they initiate the SUMO process; second, they can specifically recognize and dissociate SUMO proteins bound to substrates, a process known as deSUMOylation. However, the connection between deSUMOylation and oxidative stress remains a relatively unexplored area despite their strong association with oxidative diseases such as cancer and cardiovascular disease. This article aims to illustrate the significant contribution of SENPs to the oxidative stress pathway through deSUMOylation by reviewing their structure and classification, their roles in oxidative stress, and the changes in their expression and activity in several typical oxidative stress‐related diseases.

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