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

• DOI: 10.3389/fmolb.2024.1423594
• Publication Date: 2024-06-04T05:40:48Z
• Authors: Liangjie Sun; Yi Li; Meng Wang; Lan Luo; Ruiqing Sun; Yang Chen; Yan Bai; Chong Ding; Yixiang Wang
• Keywords: 0303 health sciences; 03 medical and health sciences; SIRT7; QH301-705.5; p53 deficiency; RRM2; crotonylation; Molecular Biosciences; cisplatin resistance; Biology (General)

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 vital cancer progression. However, the global p53-regulated crotonylome and function of these altered Kcr proteins after remain unclear. In this study, we used SILAC-based quantitative identify 3,520 1924 crotonylated response knockout. We found that increased RRM2 at K283 (RRM2K283Cr) presence promoted HCT116 cell cisplatin. discovered SIRT7 could be decrotonylase was downregulated knockout, resulting RRM2K283Cr. Mechanistically, inhibited apoptosis by upregulating protein expression RRM2K283Cr-mediated cleaved-PARP1 cleaved-caspase3 expression, upregulate upon deficiency. conclusion, our results indicated malignant colon cisplatin therapy regulating RRM2K283Cr expression. Our findings provide novel therapeutic target against p53-deficient cancer.