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Abstract
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.
Highlights
Human tumor suppressor RIZ1 (PRDM2) is encoded by the retinoblastoma protein-interacting zinc-finger gene RIZ (PRDM2), which was first identified from a functional screening for retinoblastoma tumor suppressor binding genes [1]
The expression level is almost identical between RIZ1 and RIZ2 among different human tissues except testes; and such an equivalent expression is essential for normal cell growth and functions [2,5,6]
A recent review on five candidate tumor suppressor genes, CHD5, CAMTA1, KIF1B, CASZ1 and miR-34a, located on 1p36 showed that partial impairment instead of complete inactivation of their expression was enough to promote tumorigenesis [43], implicating that downregulation of gene RIZ might follow the same mechanism in stimulating tumor development and growth
Summary
Human tumor suppressor RIZ1 (PRDM2) is encoded by the retinoblastoma protein-interacting zinc-finger gene RIZ (PRDM2), which was first identified from a functional screening for retinoblastoma tumor suppressor binding genes [1]. The silencing of RIZ1 expression is through at least one of the following four mechanisms: Methylation of the CpG islands in RIZ1 promoter. RIZ1 promoter was shown to be upregulated by silencing SMYD3 (SET and MYND domain-containing protein 3), a histone/protein methyltransferase, in human hepatoma [38] and down-regulated by silencing transcriptional repressor YY1 (Yin Yang 1) in human osteosarcoma [39]. A recent review on five candidate tumor suppressor genes, CHD5, CAMTA1, KIF1B, CASZ1 and miR-34a, located on 1p36 showed that partial impairment instead of complete inactivation of their expression was enough to promote tumorigenesis [43], implicating that downregulation of gene RIZ might follow the same mechanism in stimulating tumor development and growth.
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