Histone sumoylation and chromatin dynamics

Ryu, Hong‐Yeoul; Hochstrasser, Mark

doi:10.1093/nar/gkab280

Cited by 96 publications

(71 citation statements)

References 102 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…SUMO may be involved in the epigenetic regulation of gene expression in cancer. SUMOylation of histones is involved in regulation of chromatin dynamics [135]. SUMOylation may also influence the activity of methyltransferases, such as DNMT1, MLL1/MML2 complex and G9a [136][137][138].…”

Section: Sumoylation In Cellular Processes Relevant For Cancermentioning

confidence: 99%

Therapeutic Potential of Targeting the SUMO Pathway in Cancer

Kukkula

Ojala

Mendez

et al. 2021

Cancers

View full text Add to dashboard Cite

SUMOylation is a dynamic and reversible post-translational modification, characterized more than 20 years ago, that regulates protein function at multiple levels. Key oncoproteins and tumor suppressors are SUMO substrates. In addition to alterations in SUMO pathway activity due to conditions typically present in cancer, such as hypoxia, the SUMO machinery components are deregulated at the genomic level in cancer. The delicate balance between SUMOylation and deSUMOylation is regulated by SENP enzymes possessing SUMO-deconjugation activity. Dysregulation of SUMO machinery components can disrupt the balance of SUMOylation, contributing to the tumorigenesis and drug resistance of various cancers in a context-dependent manner. Many molecular mechanisms relevant to the pathogenesis of specific cancers involve SUMO, highlighting the potential relevance of SUMO machinery components as therapeutic targets. Recent advances in the development of inhibitors targeting SUMOylation and deSUMOylation permit evaluation of the therapeutic potential of targeting the SUMO pathway in cancer. Finally, the first drug inhibiting SUMO pathway, TAK-981, is currently also being evaluated in clinical trials in cancer patients. Intriguingly, the inhibition of SUMOylation may also have the potential to activate the anti-tumor immune response. Here, we comprehensively and systematically review the recent developments in understanding the role of SUMOylation in cancer and specifically focus on elaborating the scientific rationale of targeting the SUMO pathway in different cancers.

show abstract

Section: Sumoylation In Cellular Processes Relevant For Cancermentioning

confidence: 99%

Therapeutic Potential of Targeting the SUMO Pathway in Cancer

Kukkula

Ojala

Mendez

et al. 2021

Cancers

View full text Add to dashboard Cite

show abstract

“…SUMOylation of histones often leads to transcriptional repression either by antagonizing activating histone marks or by directly recruiting regulators with repressive activity such as histone deacetylases. Histone modification can promote the recruitment of negative regulators and this process sometimes requires SUMO/SIM interactions (reviewed in [ 49 ]). In this section, we will describe two examples of this phenomenon: one involving the SUMOylation of histone H2B [ 50 ], and another involving the SUMOylation of histone H4 [ 51 ].…”

Section: Role Of Sumo/sim Interactions In Histone Functionmentioning

confidence: 99%

SUMO Interacting Motifs: Structure and Function

Yau

Sander

Eidson

et al. 2021

Cells

View full text Add to dashboard Cite

Small ubiquitin-related modifier (SUMO) is a member of the ubiquitin-related protein family. SUMO modulates protein function through covalent conjugation to lysine residues in a large number of proteins. Once covalently conjugated to a protein, SUMO often regulates that protein’s function by recruiting other cellular proteins. Recruitment frequently involves a non-covalent interaction between SUMO and a SUMO-interacting motif (SIM) in the interacting protein. SIMs generally consist of a four-residue-long hydrophobic stretch of amino acids with aliphatic non-polar side chains flanked on one side by negatively charged amino acid residues. The SIM assumes an extended β-strand-like conformation and binds to a conserved hydrophobic groove in SUMO. In addition to hydrophobic interactions between the SIM non-polar core and hydrophobic residues in the groove, the negatively charged residues in the SIM make favorable electrostatic contacts with positively charged residues in and around the groove. The SIM/SUMO interaction can be regulated by the phosphorylation of residues adjacent to the SIM hydrophobic core, which provide additional negative charges for favorable electrostatic interaction with SUMO. The SUMO interactome consists of hundreds or perhaps thousands of SIM-containing proteins, but we do not fully understand how each SUMOylated protein selects the set of SIM-containing proteins appropriate to its function. SIM/SUMO interactions have critical functions in a large number of essential cellular processes including the formation of membraneless organelles by liquid–liquid phase separation, epigenetic regulation of transcription through histone modification, DNA repair, and a variety of host–pathogen interactions.

show abstract

“…Sumoylation involves the covalent attachment of either a single or multiple protein units among the small Ubiquitin-like modifier (SUMO) family members to histone lysines [110]. In principle, this modification could appear to be closely related and somehow redundant with respect to ubiquitylation, principally because Ubiquitin and SUMO proteins share comparable molecular size and three-dimensional structure, and both are managed by E1, E2, and E3 enzymes [111].…”

Section: Sumoylationmentioning

confidence: 99%

The Expanding Constellation of Histone Post-Translational Modifications in the Epigenetic Landscape

Cavalieri

2021

Genes

View full text Add to dashboard Cite

The emergence of a nucleosome-based chromatin structure accompanied the evolutionary transition from prokaryotes to eukaryotes. In this scenario, histones became the heart of the complex and precisely timed coordination between chromatin architecture and functions during adaptive responses to environmental influence by means of epigenetic mechanisms. Notably, such an epigenetic machinery involves an overwhelming number of post-translational modifications at multiple residues of core and linker histones. This review aims to comprehensively describe old and recent evidence in this exciting field of research. In particular, histone post-translational modification establishing/removal mechanisms, their genomic locations and implication in nucleosome dynamics and chromatin-based processes, as well as their harmonious combination and interdependence will be discussed.

show abstract

Histone sumoylation and chromatin dynamics

Cited by 96 publications

References 102 publications

Therapeutic Potential of Targeting the SUMO Pathway in Cancer

Therapeutic Potential of Targeting the SUMO Pathway in Cancer

SUMO Interacting Motifs: Structure and Function

The Expanding Constellation of Histone Post-Translational Modifications in the Epigenetic Landscape

Contact Info

Product

Resources

About