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Parkinson, D.B. et al.

Parkinson, Bhaskaran, Droggiti, Dickinson, D'Antonio, Mirsky, Jessen,

Krox-20 inhibits Jun-NH2-terminal kinase/c-Jun to control Schwann cell proliferation and death.

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 NH2-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.[1]

References

Krox-20 inhibits Jun-NH2-terminal kinase/c-Jun to control Schwann cell proliferation and death. Parkinson, D.B., Bhaskaran, A., Droggiti, A., Dickinson, S., D'Antonio, M., Mirsky, R., Jessen, K.R. J. Cell Biol. (2004) [Pubmed]

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