Journal
JOURNAL OF CELL BIOLOGY
Volume 164, Issue 3, Pages 385-394Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.200307132
Keywords
egr2; JIP-1; neuregulin; PNS; myelin
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Funding
- Wellcome Trust Funding Source: Medline
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The transcription factor Krox-20 controls Schwann cell myelination. Schwann cells in Krox-20 null mice fail to myelinate, and unlike myelinating Schwann cells, continue to proliferate and are susceptible to death. We find that enforced Krox-20 expression in Schwann cells cell-autonomously inactivates the proliferative response of Schwann cells to the major axonal mitogen beta-neuregulin-1 and the death response to TGFbeta or serum deprivation. Even in 3T3 fibroblasts, Krox-20 not only blocks proliferation and death but also activates the myelin genes periaxin and protein zero, showing properties in common with master regulatory genes in other cell types. Significantly, a major function of Krox-20 is to suppress the c-Jun NH(2)-terminal protein kinase (JNK)-c-Jun pathway, activation of which is required for both proliferation and death. Thus, Krox-20 can coordinately control suppression of mitogenic and death responses. Krox-20 also up-regulates the scaffold protein JNK-interacting protein 1 (JIP-1). We propose this as a possible component of the mechanism by which Krox-20 regulates JNK activity during Schwann cell development.
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