Crotonylation and disease: Current progress and future perspectives

Yang, Ping; Qin, Yuanyuan; Zeng, Lei; He, Yanqiu; Xie, Yumei; Cheng, Xi; Huang, Wei; Cao, Ling

doi:10.1016/j.biopha.2023.115108

Cited by 6 publications

(1 citation statement)

References 92 publications

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“…Decrotonylase includes HDAC and sirtuin family members ( Wan et al, 2019 ). Recently, significant advancements have been achieved in the exploration of both histone and nonhistone crotonylation in the contexts of infectious diseases, kidney diseases, cardiovascular diseases, metabolic diseases, spermatogenesis disorders and cancer ( Yang et al, 2023 ). Crotonylation is closely related to the occurrence and progression of colon cancer.…”

Section: Introductionmentioning

confidence: 99%

p53 deficiency mediates cisplatin resistance by upregulating RRM2 and crotonylation of RRM2K283 through the downregulation of SIRT7

Sun,

Li,

Wang

et al. 2024

Front. Mol. Biosci.

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p53 deficiency plays a crucial role in chemotherapy resistance through various biological events, including posttranslational modifications (PTMs). Recently, lysine crotonylation (Kcr) has been shown to play a vital role in cancer progression. However, the global p53-regulated crotonylome and the function of these altered Kcr proteins after p53 deficiency remain unclear. In this study, we used a SILAC-based quantitative crotonylome to identify 3,520 Kcr in 1924 crotonylated proteins in response to p53 knockout. We found that increased crotonylation of RRM2 at K283 (RRM2K283Cr) in the presence of p53 deficiency promoted HCT116 cell resistance to cisplatin. We discovered that SIRT7 could be the decrotonylase of RRM2 and was downregulated after p53 knockout, resulting in increased RRM2K283Cr. Mechanistically, p53 deficiency inhibited cell apoptosis by upregulating RRM2 protein expression and RRM2K283Cr-mediated cleaved-PARP1 and cleaved-caspase3 expression, and SIRT7 was downregulated to upregulate crotonylation of RRM2 upon p53 deficiency. In conclusion, our results indicated that p53 deficiency plays a malignant role in colon cancer resistance to cisplatin therapy by regulating RRM2 protein and RRM2K283Cr expression. Our findings provide a novel therapeutic target against p53-deficient cancer.

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Section: Introductionmentioning

confidence: 99%

p53 deficiency mediates cisplatin resistance by upregulating RRM2 and crotonylation of RRM2K283 through the downregulation of SIRT7

Sun,

Li,

Wang

et al. 2024

Front. Mol. Biosci.

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Cracking Lysine Crotonylation (Kcr): Enlightening a Promising Post‐Translational Modification

Westerveld,

Besermenji,

Aidukas

et al. 2024

ChemBioChem

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Lysine crotonylation (Kcr) is a recently discovered post‐translational modification (PTM). Both histone and non‐histone Kcr‐proteins have been associated with numerous diseases including cancer, acute kidney injury, HIV latency, and cardiovascular disease. Histone Kcr enhances gene expression to a larger extend than the extensively studied lysine acetylation (Kac), suggesting Kcr as a novel potential therapeutic target. Although numerous scientific reports on crotonylation were published in the last years, relevant knowledge gaps concerning this PTM and its regulation still remain. To date, only few selective Kcr‐interacting proteins have been identified and selective methods for the enrichment of Kcr‐proteins in chemical proteomics analysis are still lacking. The development of new techniques to study this underexplored PTM could then clarify its function in health and disease and hopefully accelerate the development of new therapeutics for Kcr‐related disease. Herein we briefly review what is known about the regulation mechanisms of Kcr and the current methods used to identify Kcr‐proteins and their interacting partners. This report aims to highlight the significant potential of Kcr as a therapeutic target and to identify the existing scientific gaps that new research must address.

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Sodium Crotonate Alleviates Diabetic Kidney Disease Partially Via the Histone Crotonylation Pathway

He,

Xie,

Zhou

et al. 2024

Inflammation

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Crotonylation and disease: Current progress and future perspectives

Cited by 6 publications

References 92 publications

p53 deficiency mediates cisplatin resistance by upregulating RRM2 and crotonylation of RRM2K283 through the downregulation of SIRT7

p53 deficiency mediates cisplatin resistance by upregulating RRM2 and crotonylation of RRM2K283 through the downregulation of SIRT7

Cracking Lysine Crotonylation (Kcr): Enlightening a Promising Post‐Translational Modification

Sodium Crotonate Alleviates Diabetic Kidney Disease Partially Via the Histone Crotonylation Pathway

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