Diversity in Post-Transcriptional Control of Neutrophil Chemoattractant Cytokine Gene Expression

In myeloid cells, chemokine mRNA instability is dependent upon AUUUA-containing ARE motifs that are recognized by TTP while in non-myeloid cells, AUUUA-free sequences produce comparable instability through undefined RNA binding protein(s). TIR signaling couples to mRNA stabilization via the adaptor protein MyD88 with IRAK4 and IRAK1 kinases, TRAF6, TAK1, and the p38 MAP kinase cascade. IL-17 signals in non-myeloid cells through the adapter protein Act1 and couples with a second mRNA stabilization pathway that operates independently of TRAF6 and p38/MK2. This second pathway also appears to be utilized by IL-1 in non-myeloid cells and segregates from the NFκB activation pathway at IRAK1. These pathways link to an instability/stabilization mechanism that depends upon non-AUUUA containing sequence and does not require TTP. The details of this second pathway, including the specific target nucleotide sequence motifs, the RNA binding proteins, and the signaling events remain to be identified.

Publication

Diversity in Post-Transcriptional Control of Neutrophil Chemoattractant Cytokine Gene Expression. () Thomas Hamilton, et al. Cytokine. ;52(1-2):116-122. Figure: F3. Homo sapiens

Disease mentions