Disease relevance of Skil

• Ubiquitin-dependent degradation of SnoN and Ski is increased in renal fibrosis induced by obstructive injury [1].
• 1-8D gene of interferon-inducible genes, Sno oncogenes, and transforming growth factor-beta II receptor were expressed in both SCC and adenocarcinoma cell lines [2].

High impact information on Skil

• The B cells, T cells and embryonic fibroblasts of sno(+/-) mice had a decreased sensitivity to apoptosis or cell cycle arrest [3].
• Mice lacking sno died at an early stage of embryogenesis, and sno was required for blastocyst formation [3].
• The sno gene, which encodes a component of the histone deacetylase complex, acts as a tumor suppressor in mice [3].
• Together, these findings suggest that Sno-dependent suppression of TGF-beta signaling is required for upregulation of growth factor production and normal T-cell proliferation following receptor ligation [4].
• These results suggest that the ski/sno protooncogenes play a role in hematopoiesis, growth factor responses, and cell cycle-regulation, with the two members of the family showing differing properties [5].

Biological context of Skil

• Proto-oncogene Sno expression, alternative isoforms and immediate early serum response [6].
• Mouse SnoN2 and SnoN are expressed throughout embryonic development, in neonatal muscle and in many adult tissues [6].
• 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 [6].
• Up-regulated transcriptional repressors SnoN and Ski bind Smad proteins to antagonize transforming growth factor-beta signals during liver regeneration [7].
• In vitro, knockdown of SnoN expression by RNA interference in tubular epithelial cells dramatically sensitized their responsiveness to TGF-beta1 stimulation [8].

Anatomical context of Skil

• Defective T-cell activation is associated with augmented transforming growth factor Beta sensitivity in mice with mutations in the Sno gene [4].
• Both ski and sno are cell cycle-regulated in synchronized factor-dependent mouse myeloid cells [5].
• Consistently, SnoN and Ski staining was diminished in the nuclei of renal tubular epithelium and interstitium after obstructive injury [8].
• Transcripts of both sno isoforms accumulate ubiquitously but are most abundant in the developing central nervous system [9].
• In contrast to Ski and Sno, which are ubiquitously expressed in human tissues, in situ hybridization, RT-PCR, Western blot and immunohistochemistry revealed a highly specific expression pattern for Fussel-18 in neuronal tissues, especially in the cerebellum, the spinal cord and dorsal root ganglia, during both embryogenesis and adult stage [10].

Analytical, diagnostic and therapeutic context of Skil

• We found that Sno mRNA is constitutively expressed in normal thymocytes and splenic T cells, with increased expression 1 h following T-cell receptor ligation [4].
• The in situ hybridization patterns of sno expression during murine development suggest potential roles in tissues with a high degree of cellular proliferation [9].

References