Hepatocellular carcinoma(HCC)is the most prevalent type of malignant liver tu-mor with high morbidity and mortality and severely threatens human health and life quality.Thus,it is of great significance to investigate ...Hepatocellular carcinoma(HCC)is the most prevalent type of malignant liver tu-mor with high morbidity and mortality and severely threatens human health and life quality.Thus,it is of great significance to investigate the molecular mechanism underlying the patho-genesis of HCC and seek biomarkers for early diagnosis.Neddylation,one of the most conserved post-translational modification types in eukaryotes,plays vital roles in the progres-sion of HCC.During the process of neddylation,NEDD8 is covalently conjugated to its substrate proteins,thereby modulating multiple necessary biological processes.Currently,increasing ev-idence shows that the aberrant activation of neddylation is positively correlated with the occurrence and development of tumors and the poor clinical prognosis of HCC patients.Based on the current investigations,neddylation modification has been reported to target both the cullins and non-cullin substrates and subsequently affect HCC progression,including the virus infection,malignant transformation,tumor cell proliferation,migration and invasion ability,and tumor microenvironment.Therefore,inhibitors targeting the neddylation cascade have been developed and entered clinical trials,indicating satisfactory anti-HCC treatment effects.This review aims to summarize the latest progress in the molecular mechanism of pathologi-cally aberrant neddylation in HCC,as well as the advances of neddylation-targeted inhibitors as potential drugs for HCC treatment.展开更多
Protein arginine methylation is a common post-translational modification involved in the regulation of various cellular functions. Coactivator-associated arginine methyltransferase 1 (CARM1) is a protein arginine meth...Protein arginine methylation is a common post-translational modification involved in the regulation of various cellular functions. Coactivator-associated arginine methyltransferase 1 (CARM1) is a protein arginine methyltransferase that asymmetrically dimethylates histone H3 and non-histone proteins to regulate gene transcription. CARM1 has been found to play important roles in cell differentiation and development, cell cycle progression, autophagy, metabolism, pre-mRNA splicing and transportation, and DNA replication. In this review, we describe the molecular characteristics of CARM1 and summarize its roles in the regulation of cell differentiation and development in mammals.展开更多
基金supported by the Natural Science Foundation of Shandong Province,China(No.ZR2021QC030,ZR2022LZL006)the Innovation Project of Shandong First Medical University.
文摘Hepatocellular carcinoma(HCC)is the most prevalent type of malignant liver tu-mor with high morbidity and mortality and severely threatens human health and life quality.Thus,it is of great significance to investigate the molecular mechanism underlying the patho-genesis of HCC and seek biomarkers for early diagnosis.Neddylation,one of the most conserved post-translational modification types in eukaryotes,plays vital roles in the progres-sion of HCC.During the process of neddylation,NEDD8 is covalently conjugated to its substrate proteins,thereby modulating multiple necessary biological processes.Currently,increasing ev-idence shows that the aberrant activation of neddylation is positively correlated with the occurrence and development of tumors and the poor clinical prognosis of HCC patients.Based on the current investigations,neddylation modification has been reported to target both the cullins and non-cullin substrates and subsequently affect HCC progression,including the virus infection,malignant transformation,tumor cell proliferation,migration and invasion ability,and tumor microenvironment.Therefore,inhibitors targeting the neddylation cascade have been developed and entered clinical trials,indicating satisfactory anti-HCC treatment effects.This review aims to summarize the latest progress in the molecular mechanism of pathologi-cally aberrant neddylation in HCC,as well as the advances of neddylation-targeted inhibitors as potential drugs for HCC treatment.
基金supported by Funding for Top-notch Personnel from Shandong First Medical University and Taishan Scholars Program(No.ts 2019097).
文摘Protein arginine methylation is a common post-translational modification involved in the regulation of various cellular functions. Coactivator-associated arginine methyltransferase 1 (CARM1) is a protein arginine methyltransferase that asymmetrically dimethylates histone H3 and non-histone proteins to regulate gene transcription. CARM1 has been found to play important roles in cell differentiation and development, cell cycle progression, autophagy, metabolism, pre-mRNA splicing and transportation, and DNA replication. In this review, we describe the molecular characteristics of CARM1 and summarize its roles in the regulation of cell differentiation and development in mammals.
