SKI (SKI proto-oncogene)
The SKI gene, formally designated as the Sloan-Kettering Institute proto-oncogene, encodes a member of the SKI/SnoN protein family, which functions as critical negative regulators of the transforming growth factor-beta (TGF-β) signaling pathway. By directly interacting with the Smad2/3/4 transcriptional complexes, SKI inhibits the downstream transcriptional activities of these key signal transducers, thereby blocking TGF-β-mediated effects on cell cycle arrest, apoptosis, and differentiation. This regulatory role is pivotal during embryonic development, particularly in governing neural crest cell migration and skeletal muscle formation, where precise modulation of TGF-β signaling is required. In the context of disease, gain-of-function mutations, such as truncations that enhance protein stability, or somatic overexpression of SKI can lead to excessive suppression of the TGF-β pathway, resulting in the downregulation of tumor suppressors like CDKN1A/p21 and the promotion of uncontrolled cellular proliferation, a mechanism implicated in the pathogenesis of melanoma, leukemia, and other malignancies. Conversely, loss-of-function mutations or low expression levels can cause hyperactivation of TGF-β signaling, potentially leading to developmental defects, fibrotic conditions such as pulmonary fibrosis, or autoimmune responses. The SKI and SnoN proteins exhibit functional redundancy, collectively fine-tuning TGF-β homeostasis to maintain normal tissue architecture while preventing pathological states associated with either insufficient or excessive pathway activity.
Gene Ontology
Subcellular localization of SKI (and its protein):
- plasma membrane
- cytoplasm
- extracellular
- golgi
- vesicle
- cytoskeleton
- endoplasmic reticulum
- nucleus
- endosome
- lysosome
- mitochondrion
Gene Ontology (GO) terms for SKI:
| Interacting Gene | Interaction | Source/Score |
| Name |
|---|
| Downregulation of SMAD2/3:SMAD4 transcriptional activity |
| Gene Expression |
| Generic Transcription Pathway |
| Signaling by BMP |
| Signaling by TGF-beta Receptor Complex |
| Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer |
| Disease | Score | NofPmids | NofSnps | Source |
| Shprintzen-Goldberg syndrome | 0.481085767 | 4 | 8 | BeFree_CLINVAR_CTD_human_ORPHANET_UNIPROT |
| Chromosome 1p36 Deletion Syndrome | 0.120542884 | 2 | 0 | BeFree_ORPHANET |
| Aortic Aneurysm | 0.120271442 | 1 | 0 | BeFree_CTD_human |
| Congenital musculoskeletal anomalies | 0.12 | 1 | 0 | CTD_human |
| Craniofacial Abnormalities | 0.12 | 1 | 0 | CTD_human |
| Neural Tube Defects | 0.12 | 1 | 0 | CTD_human |
| melanoma | 0.010073144 | 8 | 0 | BeFree_LHGDN |
| Anophthalmos | 0.005091382 | 1 | 0 | GAD_LHGDN |
| Cleft Palate | 0.004734064 | 2 | 0 | GAD |
| Cleft Lip | 0.004734064 | 2 | 0 | GAD |
Contact
No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong
Qilu Normal University · Genelibs Bioinformatics Lab
750 Shunhua Rd, Jinan
2F, Bldg F, University Science Park
Tel: 0531-88819269
WeChat Official Account
Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.
Business Email
E-mail: [email protected]
Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2
