Shanghai Jiaotong Daxue xuebao. Yixue ban (Jan 2023)
A review of RIZ1 regulation of the signal pathways in obesity and tumors
Abstract
Retinoblastoma-interacting zinc finger protein 1 (RIZ1) gene, also known as positive regulatory domain 2 (PRDM2), is a member of the PRDM gene family whose protein sequence consists of a PR domain, a nuclear hormone receptor binding motif, eight zinc finger domains, and an Rb (retinoblastoma protein) interacting motif. RIZ1 is mainly localized in the nucleus, where it plays a role in transcriptional repressor, gene regulation, protein-protein interactions, and other functions. RIZ1 is an important participant in the metabolic pathway, which affects basal metabolism and inhibits the development of obesity by regulating metabolism-related genes; functional mutations or insufficient content of RIZ1 are associated with the development of a variety of tumors, which participate in tumor processes by activating downstream oncogenes or regulating metabolism. RIZ1 regulates three molecular signal pathways, AKT (v-akt murine thymoma viral oncogene homolog)/mTOR (mechanistic target of rapamycin kinase), IGF-1 (insulin-like growth factor 1), and estrogen, in tumors and obesity through AKT3 and IGF-1, respectively, or acting as a co-activator. The functional differences of the three molecular pathways and the crossover of their downstream molecules suggest that RIZ1 may function differently in different ages, genders, and organs. The study of the regulatory role of RIZ1 and RIZ2 in metabolic processes can help to fully understand the mechanism of RIZ1 involvement in obesity and tumor formation. In the future, diagnostic research or functional recovery based on RIZ1 targets may be of great significance for the diagnosis and treatment of metabolic diseases and tumor.
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