The putative tumor suppressor Zc3h12d modulates toll-like receptor signaling in macrophages

Shengping Huang, Dongfei Qi, Jian Liang, Ruidong Miao, Kentaro Minagawa, Tim Quinn, Toshimitsu Matsui, Daping Fan, Jianguo Liu, Mingui Fu

Research output: Contribution to journalArticlepeer-review

39 Scopus citations


Toll-like receptors (TLR) are pivotal in macrophage activation. The molecular mechanisms controlling TLR signaling and macrophage activation are not completely understood. Zc3h12d is originally identified as a possible tumor suppressor gene. However, its function remains unknown. We here report that Zc3h12d negatively regulates TLR signaling and macrophage activation. Zc3h12d was enriched in spleen, lung and lymph node. In macrophages, the expression of Zc3h12d was remarkably induced by TLR ligands through JNK and NF-κB signal pathways. On the other hand, overexpression of Zc3h12d significantly inhibited TLR2 and TLR4 activation-induced JNK, ERK and NF-κB signaling as well as macrophage inflammation. Similar to Zc3h12a/MCPIP1, Zc3h12d also decreased the global cellular protein ubiquitination. These findings suggest that Zc3h12d is a novel negative feedback regulator of TLR signaling and macrophage activation and thus may play a role in host immunity and inflammatory diseases.

Original languageEnglish (US)
Pages (from-to)569-576
Number of pages8
JournalCellular Signalling
Issue number2
StatePublished - Feb 2012

All Science Journal Classification (ASJC) codes

  • Cell Biology


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