AA28-67 domain within MyD88 suppresses c-myc activity and expression to regulate differentiation and function of dendritic cells

作者：Zhang Zhuohan; Zeng Bin; Jiao Guohui; Li Yuhao; Liu Yu; Zhang Yuan; Yang Rongcun^*

来源：Clinical Immunology, 2009, 133(3): 324-332.

DOI：10.1016/j.clim.2009.08.005

• c-myc
• Signal transduction
• Molecular biology

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-kappa B 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-kappa B and MAPK but also via suppressing c-myc activity and expression.

• 出版日期2009-12
• 单位南开大学