AA28-67 domain within MyD88 suppresses c-myc activity and expression to regulate differentiation and function of dendritic cells
The mechanism by which c-myc expression in undifferentiated cells rapidly declines following induction of differentiation is poorly characterized. We demonstrate here that MyD88, which can activate NF-kappaB and MAPK, also suppresses c-myc activity and expression. The aa 28-67 domain, a highly conse...
| Publié dans: | Clinical immunology (Orlando, Fla.). - 1999. - 133(2009), 3 vom: 15. Dez., Seite 324-32 |
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| Auteur principal: | |
| Autres auteurs: | , , , , , |
| Format: | Article en ligne |
| Langue: | English |
| Publié: |
2009
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| Accès à la collection: | Clinical immunology (Orlando, Fla.) |
| Sujets: | Journal Article Research Support, Non-U.S. Gov't Myc protein, mouse Myd88 protein, mouse Myeloid Differentiation Factor 88 Proto-Oncogene Proteins c-myc RNA, Small Interfering RNA 63231-63-0 |
| Résumé: | The mechanism by which c-myc expression in undifferentiated cells rapidly declines following induction of differentiation is poorly characterized. We demonstrate here that MyD88, which can activate NF-kappaB and MAPK, also suppresses c-myc activity and expression. The aa 28-67 domain, a highly conserved region within MyD88, plays a critical role in the MyD88-mediated inhibition. Indeed, deletion of the aa 28-67 domain (MyD88 Delta 28-67) or mutation of the highly conserved amino acid residue phenylalanine (aa 36) to aspartic acid (MyD88 Delta F36D) significantly promoted c-myc activity and expression. Additionally, we found that MyD88 Delta 28-67-mediated c-myc activity and expression could be abrogated using PI3K inhibitor, suggesting that the PI3K/Akt signaling pathway may be involved in MyD88-mediated suppression of c-myc. Compared to MyD88-transduced DCs, MyD88 Delta 28-67- and MyD88 Delta F36D-transduced DCs derived from MyD88-/- bone marrow cells had lower antigen-presenting ability. Thus, MyD88 induces the differentiation and maturation of DCs not only by activating NF-kappaB and MAPK but also via suppressing c-myc activity and expression |
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| Description: | Date Completed 22.12.2009 Date Revised 09.11.2009 published: Print-Electronic Citation Status MEDLINE |
| ISSN: | 1521-7035 |
| DOI: | 10.1016/j.clim.2009.08.005 |