O-GlcNAcylation and stablization of SIRT7 promote pancreatic cancer progression by blocking the SIRT7-REGγ interaction

• DOI: 10.1038/s41418-022-00984-3
• Publication Date: 2022-04-14T19:02:59Z
• Authors: Xiaoman He; Yongzhou Li; Qing Chen; Lei Zheng; Jianyao Lou; Chuanshuai Lin; Jiali Gong; Yi Zhu; Yulian Wu
• Keywords: 0301 basic medicine; Proteasome Endopeptidase Complex; N-Acetylglucosaminyltransferases; NAD; Autoantigens; Article; 3. Good health; Pancreatic Neoplasms; 03 medical and health sciences; Serine; Humans; Sirtuins; Protein Processing, Post-Translational; Carcinoma, Pancreatic Ductal; Cell Proliferation

Abstract Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers and its dismal prognosis indicates urgent need to elucidate potential oncogenic mechanisms. SIRT7 a classic NAD + -dependent deacetylase that stabilizes transformed state cancer cells. However, functional roles in PDAC are still unclear. Here, we found expression upregulated predicts poor PDAC. Then screened new interacting proteins by mass spectrometry results showed can interact with O-GlcNAc transferase (OGT). O-GlcNAcylation protein inhibiting interaction REGγ prevent degradation, hyper-O-GlcNAcylation pancreatic cells leads hypoacetylation H3K18 via SIRT7, which promotes transcriptional repression several tumour suppressor genes. In addition, at serine 136 residue (S136) required maintain stability deacetylation ability. vivo vitro experiments blocking S136 attenuates progression. Collectively, demonstrate an important post-translational modification cells, elucidating this mechanism expected pave way for development novel therapeutic methods future.