Total Chemical Synthesis of Modified Histones

Qi, Yun‐Kun; Ai, Huasong; Li, Yiming; Yan, Baihui

doi:10.3389/fchem.2018.00019

Cited by 32 publications

(22 citation statements)

References 89 publications

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“…It is also key to determine the primary and secondary effects of the histone mutations. New advances in development of tools for in vitro assessment of the roles of histone mutations, post-translational modifications [135], and the use of temporal control of mutant histone expression in cells, will be instrumental for a full understanding of histone biology and its contribution to cancer.…”

Section: Conclusion and The Future For Histone Mutant Research Inmentioning

confidence: 99%

Histone H3 Mutations: An Updated View of Their Role in Chromatin Deregulation and Cancer

Lowe

Maxham

Hamey

et al. 2019

Cancers

101

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In this review, we describe the attributes of histone H3 mutants identified in cancer. H3 mutants were first identified in genes encoding H3.3, in pediatric high-grade glioma, and subsequently in chondrosarcomas and giant cell tumors of bone (GCTB) in adolescents. The most heavily studied are the lysine to methionine mutants K27M and K36M, which perturb the target site for specific lysine methyltransferases and dominantly perturb methylation of corresponding lysines in other histone H3 proteins. We discuss recent progress in defining the consequences of these mutations on chromatin, including a newly emerging view of the central importance of the disruption of H3K36 modification in many distinct K to M histone mutant cancers. We also review new work exploring the role of H3.3 G34 mutants identified in pediatric glioma and GCTB. G34 is not itself post-translationally modified, but G34 mutation impinges on the modification of H3K36. Here, we ask if G34R mutation generates a new site for methylation on the histone tail. Finally, we consider evidence indicating that histone mutations might be more widespread in cancer than previously thought, and if the perceived bias towards mutation of H3.3 is real or reflects the biology of tumors in which the histone mutants were first identified.

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Section: Conclusion and The Future For Histone Mutant Research Inmentioning

confidence: 99%

Histone H3 Mutations: An Updated View of Their Role in Chromatin Deregulation and Cancer

Lowe

Maxham

Hamey

et al. 2019

Cancers

101

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“…The chemoselective reaction between peptides containing C-terminal thioesters and N-terminal Cys, known as ''native chemical ligation (NCL)'' (Dawson and Kent, 2000), has enabled the synthesis of small to medium-sized proteins (Zheng et al, 2013). Many Lys PTMs have been successfully installed, especially those two challenging groups as K Me3 and K Ub , particularly in the context of histones (Qi et al, 2018).…”

Section: Chemoselective Ligationsmentioning

confidence: 99%

The Chemical Biology of Reversible Lysine Post-translational Modifications

Wang

Cole

2020

Cell Chemical Biology

102

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Lysine (Lys) residues in proteins undergo a wide range of reversible post-translational modifications (PTMs), which can regulate enzyme activities, chromatin structure, protein-protein interactions, protein stability, and cellular localization. Here we discuss the ''writers,'' ''erasers,'' and ''readers'' of some of the common protein Lys PTMs and summarize examples of their major biological impacts. We also review chemical biology approaches, from small-molecule probes to protein chemistry technologies, that have helped to delineate Lys PTM functions and show promise for a diverse set of biomedical applications. ll

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“…Ub conjugates incorporating isopeptide bond mimetics can also be synthesized from the expressed Ub [70][71][72][73]84,85 (Fig. 7).…”

Section: Biorthogonal Synthesis Of Mimic Ub Conjugatesmentioning

confidence: 99%