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Krox-20 conducts the Schwann song

Krox-20 makes fibroblasts turn on myelin genes.

When Schwann cells begin to myelinate large-diameter axons, they stop dividing, become resistant to apoptosis, and start producing myelin proteins. How are all of these changes coordinated? On page 385, Parkinson et al. identify several new signaling interactions in Schwann cells, and show that the transcription factor Krox-20 is a master regulator of myelination.

The authors found that Krox-20 expression makes Schwann cells resistant to the mitogen NRG-1 and the apoptosis-inducing action of TGF-ß. Rather than specifically targeting these signaling molecules, Krox-20 appears to act through a general mechanism, suppressing the activity of the JNK/c-Jun pathway. The data show that JNK/c-Jun signaling is required for both proliferative and apoptotic responses in Schwann cells. Krox-20 expression increases the expression of the scaffold protein JIP-1, a known inhibitor of JNK activity, and also decreases the level of c-Jun protein in the cell, providing two possible ways to inhibit JNK/c-Jun signals.

Surprisingly, expression of Krox-20 in cultured 3T3 fibroblasts, which are not related to Schwann cells, causes the fibroblasts to stop dividing, resist apoptosis, and express the myelin genes periaxin and P₀. The ability to induce so many specialized responses in a different cell type indicates that Krox-20 is a master regulator.

By turning off a single pathway that is activated by both NRG-1 and TGF-ß, Krox-20 can coordinate changes in both proliferative and apoptotic activities without affecting other processes activated by growth factors. Its position as a master regulator explains why mutations in Krox-20 often lead to severe hereditary myelination disorders. Parkinson et al. are now trying to determine whether Krox-20 acts directly or indirectly to reduce c-Jun levels and induce myelin gene expression.

Alan W. Dove

alanwdove{at}earthlink.net

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

David B. Parkinson, Ambily Bhaskaran, Anna Droggiti, Sarah Dickinson, Maurizio D'Antonio, Rhona Mirsky, and Kristjan R. Jessen
J. Cell Biol. 2004 164: 385-394. [Abstract] [Full Text] [PDF]

This Article Full Text (PDF, 421K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Dove, A. W. Search for Related Content PubMed Articles by Dove, A. W. Related Collections Related Article Social Bookmarking                            What's this?