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PMID:15312649

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Citation

Atanasoski, S, Notterpek, L, Lee, HY, Castagner, F, Young, P, Ehrengruber, MU, Meijer, D, Sommer, L, Stavnezer, E, Colmenares, C and Suter, U (2004) The protooncogene Ski controls Schwann cell proliferation and myelination. Neuron 43:499-511

Abstract

Schwann cell proliferation and subsequent differentiation to nonmyelinating and myelinating cells are closely linked processes. Elucidating the molecular mechanisms that control these events is key to the understanding of nerve development, regeneration, nerve-sheath tumors, and neuropathies. We define the protooncogene Ski, an inhibitor of TGF-beta signaling, as an essential component of the machinery that controls Schwann cell proliferation and myelination. Functional Ski overexpression inhibits TGF-beta-mediated proliferation and prevents growth-arrested Schwann cells from reentering the cell cycle. Consistent with these findings, myelinating Schwann cells upregulate Ski during development and remyelination after injury. Myelination is blocked in myelin-competent cultures derived from Ski-deficient animals, and genes encoding myelin components are downregulated in Ski-deficient nerves. Conversely, overexpression of Ski in Schwann cells causes an upregulation of myelin-related genes. The myelination-regulating transcription factor Oct6 is involved in a complex modulatory relationship with Ski. We conclude that Ski is a crucial signal in Schwann cell development and myelination.

Links

PubMed Online version:10.1016/j.neuron.2004.08.001

Keywords

Animals; Cell Cycle/genetics; Cell Division/genetics; Cells, Cultured; DNA-Binding Proteins/biosynthesis; DNA-Binding Proteins/deficiency; DNA-Binding Proteins/genetics; DNA-Binding Proteins/physiology; Gene Expression Regulation/physiology; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Mutant Strains; Mice, Transgenic; Myelin Sheath/genetics; Myelin Sheath/physiology; Proto-Oncogene Proteins/biosynthesis; Proto-Oncogene Proteins/deficiency; Proto-Oncogene Proteins/genetics; Proto-Oncogene Proteins/physiology; Proto-Oncogenes/physiology; Rats; Rats, Wistar; Schwann Cells/cytology; Schwann Cells/metabolism; Sciatic Nerve/cytology; Sciatic Nerve/metabolism; Transfection

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:SKI

acts_upstream_of_or_within

GO:0030512: negative regulation of transforming growth factor beta receptor signaling pathway

ECO:0000316: genetic interaction evidence used in manual assertion

UniProtKB:P01137

P

Seeded From UniProt

complete

HUMAN:SKI

acts_upstream_of_or_within

GO:0010626: negative regulation of Schwann cell proliferation

ECO:0000316: genetic interaction evidence used in manual assertion

UniProtKB:P01137

P

Seeded From UniProt

complete

MOUSE:SKI

acts_upstream_of_or_within

GO:0022011: myelination in peripheral nervous system

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2177555

P

  • occurs_in:(EMAPA:32815)

Seeded From UniProt

complete


See also

References

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