JCB logo
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published 2 February 2004. doi:10.1083/jcb.200307132
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 164, Number 3, 385-394
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 428K)
Right arrow PPT slides of all figures
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JCB
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Parkinson, D. B.
Right arrow Articles by Jessen, K. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Parkinson, D. B.
Right arrow Articles by Jessen, K. R.
Related Collections
Right arrowRelated Article
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Article

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

Department of Anatomy and Developmental Biology, University College London, London WC1E 6BT, UK

Address correspondence to David B. Parkinson, Department of Anatomy and Developmental Biology, University College London, Gower Street, London, WC1E 6BT UK. Tel.: 44-20-7679-3365. Fax: 44-20-7679-2091. email: david.parkinson{at}ucl.ac.uk

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 ß–neuregulin-1 and the death response to TGFß 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.

Key Words: egr2; JIP-1; neuregulin; PNS; myelin

Abbreviations used in this paper: DM, defined medium; JBD, JNK binding domain; JIP-1, JNK-interacting protein 1; JNK, c-Jun NH2-terminal protein kinase; NRG-1, ß-neuregulin-1; P0, protein zero.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?

Related Article

Krox-20 conducts the Schwann song
Alan W. Dove
J. Cell Biol. 2004 164: 332-333. [Full Text] [PDF]



This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents