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PNAS 108 (43): 17749-17754

Copyright © 2011 by the National Academy of Sciences.

BIOLOGICAL SCIENCES / IMMUNOLOGY

A role for c-Myc in regulating anti-mycobacterial responses

Howard C. H. Yim, James C. B. Li, John C. H. Pong, and Allan S. Y. Lau1

Cytokine Biology Group, Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China

Edited by Tak Wah Mak, The Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute at Princess Margaret Hospital, University Health Network, Toronto, Canada, and approved September 19, 2011 (received for review April 7, 2011)

Abstract: c-Myc (Myc) is a well known transcription factor that regulates many essential cellular processes; however, its role in modulating immunity is not known. Here, we showed different species of mycobacteria can induce Myc expression via ERK1/2 and JNK activation. Unexpectedly, the induced Myc is localized in the cytoplasm but not in the nucleus. This induced Myc expression is associated with the induction of TNF-α and IL-6 and with the suppression of intracellular mycobacterial growth. To delineate the underlying mechanisms, we demonstrated that Myc enhances IRAK1 degradation, leading to specific activations of ERK1/2 and p38 MAPK but not Akt, and reduces I{kappa}Bα protein recovery upon degradation. Hence, our findings may provide insights into a potential role for Myc in regulating the antimicrobial responses.

Key Words: cytokine • macrophages

Author contributions: H.C.H.Y., J.C.B.L., and A.S.Y.L. designed research; H.C.H.Y. and J.C.H.P. performed research; H.C.H.Y., J.C.B.L., and A.S.Y.L. analyzed data; and H.C.H.Y. wrote the paper.

The authors declare no conflict of interest.

This article is a PNAS Direct Submission.

This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1104892108/-/DCSupplemental.

1To whom correspondence should be addressed. E-mail: asylau{at}hku.hk.

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