| First Author | Zhang Z | Year | 2009 |
| Journal | Clin Immunol | Volume | 133 |
| Issue | 3 | Pages | 324-32 |
| PubMed ID | 19740707 | Mgi Jnum | J:155240 |
| Mgi Id | MGI:4413386 | Doi | 10.1016/j.clim.2009.08.005 |
| Citation | Zhang Z, et al. (2009) AA28-67 domain within MyD88 suppresses c-myc activity and expression to regulate differentiation and function of dendritic cells. Clin Immunol 133(3):324-32 |
| abstractText | 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. |
