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Ski-like proto-oncogene (SKIL)
- Target
- SKIL
- Molecular classification
- Transcription factor, Transcriptional corepressor, SMAD pathway regulator
01
Overview
Ski-like proto-oncogene (SKIL) encodes the Ski-like protein (SnoN/SNON), a nuclear transcriptional co-repressor that regulates transforming growth factor-beta (TGF-β)/SMAD signaling by binding to SMAD complexes and recruiting additional corepressors, such as histone deacetylases, to inhibit gene expression. SKIL is a member of the Ski/Sno/Dac family and acts in diverse cellular processes, including cell proliferation, cell cycle arrest, differentiation, and extracellular matrix regulation. By repressing or coactivating transcription in a context-dependent manner, SKIL influences normal development and tissue homeostasis, and dysregulation is associated with various cancers and genetic syndromes such as Shprintzen-Goldberg syndrome. The SKIL gene is implicated as both a proto-oncogene and tumor suppressor, depending on tissue context and interacting factors.
- Other names
- Ski-like proteinSNONSnoNSnoASki-related oncogeneSki-related proteinSNOSnoISKI-like oncogeneski-related oncogene snoNSKILv-ski avian sarcoma viral oncogene homolog
02
Mechanism of action
Direct/indirect modulation of TGF-β/SMAD signaling Transcriptional corepression and gene silencing (via recruitment of HDACs/corepressors) Protein-protein interactions affecting gene regulation and cellular responses
03
Biological functions
Regulation of TGF-β/SMAD signalingTranscriptional repression (by recruiting corepressors)Modulation of cell growth and differentiationCell cycle arrestCell proliferationExtracellular matrix gene expressionInhibition of gene expression via histone deacetylationSilencing of specific genes (including own gene)Coactivation of nuclear receptors
04
Disease associations
Cancer (multiple types: breast, colorectal, esophageal squamous, pancreatic, lung, acute myeloid leukemia)Shprintzen-Goldberg syndrome (genetic disorder with developmental symptoms)Prostate cancerObstructive nephropathyOther context-dependent roles in cell transformation and tumor suppression
05
Safety considerations
Therapeutic targeting risks disrupting essential cell-cycle regulation or differentiationPotential for off-target metabolic or developmental effects due to broad role in transcription regulationLimited druggability as a nuclear transcription factor/co-repressor
06
Interacting drugs
P144 peptide (TGF-β inhibitory peptide, experimental)
07
Biomarkers
Ski-like proto-oncogene expression (as negative/positive prognostic marker in cancers)Ski/SnoN gene methylation (lung cancer prognosis)Two-gene signature (SKIL and Slamf1 in chronic lymphocytic leukemia)High cytoplasmic Ski as a positive survival marker (breast cancer)
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