Editors' ChoiceHost-Pathogen Interactions

Myc Against Mycobacteria

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Science Signaling  01 Nov 2011:
Vol. 4, Issue 197, pp. ec308
DOI: 10.1126/scisignal.4197ec308

The transcription factor Myc is normally localized in the nucleus, where it activates transcription of target genes. Yim et al. uncovered a role for cytoplasmic Myc in potentiating the immune response to various strains of the pathogenic bacteria Mycobacteria, including the strain that causes tuberculosis. In immune cells that recognize mycobacteria, interleukin 1 (IL-1) receptor–associated kinases (IRAK) 1 and 4 are activated, which leads to degradation of IκBα [inhibitor of nuclear factor κB (NF-κB)]. Consequently, the transcription factor NF-κB activates transcription of genes encoding inflammatory cytokines, such as tumor necrosis factor–α (TNF-α) and IL-6. In addition, mitogen-activated protein kinases (MAPKs) also promote the expression of genes involved in the immune response. The authors found that infection of primary human macrophages with various strains of mycobacteria resulted in increased protein abundance of Myc, an effect that correlated with the concentration of mycobacteria. The increase in Myc mRNA abundance required the activity of extracellular signal–regulated kinase (ERK) 1 or 2 and c-Jun N-terminal kinase (JNK) 1 or 2. In mycobacteria-infected macrophages, Myc was localized to the cytoplasm, and infection elicited increased production of TNF-α and IL-6, degradation of IRAK1, increased phosphorylation of ERK1/2 and p38, and decreased IκBα abundance, effects that were reduced by transfection of cells with short interfering RNAs (siRNAs) directed against Myc. In addition, mycobacterial growth was increased in macrophages transfected with Myc-specific siRNAs. Overexpression of Myc in macrophages increased TNF-α production and decreased IRAK-1 abundance. The mechanisms by which cytoplasmic Myc promotes antimycobacterial responses in macrophages remain to be determined.

H. C. H. Yim, J. C. B. Li, J. C. H. Pong, A. S. Y. Lau, A role for c-Myc in regulating anti-mycobacterial responses. Proc. Natl. Acad. Sci. U.S.A. 108, 17749–17754 (2011). [Abstract] [Full Text]

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