Журнал канцерогенеза и мутагенеза

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Tumor Suppressor RIZ1 in Carcinogenesis

Wanpeng Sun and Jian Yang

Human retinoblastoma protein-interacting zinc-finger gene RIZ (PRDM2) encodes two protein products, tumor suppressor RIZ1 and proto-oncoprotein RIZ2, using alternative promoters. RIZ1 and RIZ2 regulate normal cell division in a Yin-Yang fashion with RIZ1 arresting cells in G2/M phase and inducing apoptosis and RIZ2 promoting cell proliferation. Silenced RIZ1 expression has been detected in various types of cancer. Because both RIZ isoforms contain multiple functional domains, their function mechanisms in suppressing or promoting tumor growth are complex. Based on the current knowledge, it is rational to propose four potential routes for RIZ1 to exert its tumor suppressing functions: directly repressing the promoters of growth factors such as insulin-like growth factor-1 via H3K9 (histone H3 lysine 9) methylation, regulating estrogen-induced pS2 transcription through forming a complex with transcriptional co-activator p300, activating tumor suppressor p53 using a methylation-acetylation interplay, and blocking gene transcriptions by binding to PR-Set7 and establishing a H4K20me1 (histone H4 lysine 20 monomethylation) - H3K9me1 (histone H3 lysine 9 mono-methylation) trans-tail ‘histone code’ at an ectopic locus.