Abstract
The staphylococcal nuclease and tudor domain containing 1 (SND1) is a multifunctional protein overexpressed in breast, prostate, colorectal and hepatocellular carcinomas and malignant glioma. Molecular studies have revealed the multifaceted activities of SND1 involved in regulating gene expression at transcriptional as well as post-transcriptional levels. Early studies identified SND1 as a transcriptional co-activator. SND1 is also a component of RNA-induced silencing complex (RISC) thus mediating RNAi function, a regulator of mRNA splicing, editing and stability, and plays a role in maintenance of cell viability. Such diverse actions allow the SND1 to modulate a complex array of molecular networks, thereby promoting carcinogenesis. Here, we describe the crucial role of SND1 in cancer development and progression, and highlight SND1 as a potential target for therapeutic intervention.
Highlights
The staphylococcal nuclease and tudor domain containing 1 (SND1) is a multifunctional protein overexpressed in breast, prostate, colorectal and hepatocellular carcinomas and malignant glioma
Our studies have shown that astrocyte elevated gene-1 (AEG1), an important oncogene (36,37), in association with SND1 and other proteins, forms a stable RNA-induced silencing complex (RISC) complex (12)
The reverse finding was observed upon knockdown of SND1 or AEG-1 (12). These findings suggest that increased RISC activity conferred by SND1 and AEG-1 might contribute to the carcinogenic process (12)
Summary
The human SND1 gene was assigned to chromosome 7q31.3 band location employing restriction fragment and fluorescence in situ hybridization (FISH) analyses (21). Human SND1 is a 910-a.a. containing protein with highly conserved domains found even in Caenorhabditis elegans. The nuclease domains share 20-30% sequence homology (3) These domains have been well characterized and found to be structurally related to staphylococcal nuclease (SN) domains (3). These are thermonucleases that hydrolyze DNA and RNA in a calciumdependent manner (3). Tudor domain containing proteins are involved in DNA interactions, in epigenetic regulation, gene expression as well as snRNP, miRNA and siRNA biogenesis (26). The presence of these versatile SN and Tudor domains confer SND1 with its diverse multifunctional properties (Fig. 2)
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