Oligoribonuclease (Orn) is a DEDDh-type DnaQ-like 3'-5' exoribonuclease that is responsible for degrading small oligoribonucleotides to mononucleotides. It contains three conserved sequence motifs termed ExoI, ExoII and ExoIII, with a specific Hx(4)D conserved pattern at ExoIII. These motifs are clustered around the active site and contain four conserved acidic residues that serve as ligands for the two metal ions required for catalysis. Orn is essential for Escherichia coli survival []. The human homologue, also called Sfn (small fragment nuclease), is able to hydrolyse short single-stranded RNA and DNA oligomers. It plays a role in cellular nucleotide recycling [, ].
14-3-3 protein sigma isoform, also known as stratifin or human mammary epithelial marker (HME) 1, has been most directly linked to tumour development [, ]. In humans, it is expressed by the SFN gene, strictly in stratified squamous epithelial cells in response to DNA damage where it is transcriptionally induced in a p53-dependent manner, subsequently causing cell-cycle arrest at the G2/M checkpoint []. Up-regulation and down-regulation of 14-3-3 sigma expression have both been described in tumours. For example, in human breast cancer, 14-3-3 sigma is predominantly down-regulated by CpG methylation, acting as both a tumour suppressor and a prognostic indicator [], while in human scirrhous-type gastric carcinoma (SGC), it is up-regulated and may play an important role in SGC carcinogenesis and progression []. Loss of 14-3-3 sigma expression sensitizes tumour cells to treatment with conventional cytostatic drugs, making this protein an attractive therapeutic target [].
