Proto-oncogene Sno expression, alternative isoforms and immediate early serum response

Abstract

The mouse Sno gene, a Ski proto-oncogene homolog, expresses two isoforms, SnoN and SnoN2 (also called sno -dE3), which differ from each other in a location downstream from the site of alternative splicing previously described in the human SNO gene. SnoN2 is missing a 138 nt coding segment present in mouse SnoN and human SNON . We have cloned and sequenced the human ortholog of mouse SnoN2 , the existence of which was predicted from conservation of the alternative splice donor site that produces the SnoN2 isoform. Mouse SnoN2 and SnoN are expressed throughout embryonic development, in neonatal muscle and in many adult tissues. SnoN2 is the major species in most tissues, but SnoN and SnoN2 are expressed at approximately equal levels in brain. In human tissues, SNON2 is the less abundantly expressed isoform. Expression of mouse SnoN and SnoN2 mRNAs is induced with immediate early kinetics upon serum stimulation of quiescent fibroblasts, even in the presence of the protein synthesis inhibitor cycloheximide, while Ski is not. Interestingly, although both isoforms of Sno are induced, SnoN2 induction is much higher than SnoN . These data are consistent with a role for Sno in the response to proliferation stimuli.

Up-regulated Transcriptional Repressors SnoN and Ski Bind Smad Proteins to Antagonize Transforming Growth Factor-β Signals during Liver Regeneration

“…In contrast, the two main bands of Ski mRNA (4.7 and 6.0 kb) were induced at later stages of regeneration (0 h ϭ 1-fold and 48 h ϭ 2-fold induction) ( Fig. 2A), showing that ski is a delayed-early gene as previously described (30,31).…”

TIF1γ Protein Regulates Epithelial-Mesenchymal Transition by Operating as a Small Ubiquitin-like Modifier (SUMO) E3 Ligase for the Transcriptional Regulator SnoN1

“…SnoN is the product of the Sno (Ski-related novel) gene. SnoN1 and SnoN2 represent the two major alternatively spliced isoforms of SnoN that are nearly identical except for a 46-amino acid region that is present in SnoN1 and absent in SnoN2 (22). In the nervous system, SnoN1 and SnoN2 play opposing roles in the control of neuronal migration (21), a biological process with parallels to EMT (23,24).…”

SnoN Is a Cell Type-specific Mediator of Transforming Growth Factor-β Responses

“…1C). For mouse SnoN, we used an expression vector encoding the alternatively spliced isoform SnoN2 that is the most abundant isoform in mouse and that is identical to SnoN1 except for the absence of nucleotides 1280 -1417 (49). In these experiments we found that the ex- (Fig.…”