例如:"lncRNA", "apoptosis", "WRKY"

An Evolutionarily Conserved PLC-PKD-TFEB Pathway for Host Defense.

Cell Rep. 2016 May 24;15(8):1728-42. Epub 2016 May 12
Mehran Najibi 1 , Sid Ahmed Labed 1 , Orane Visvikis 1 , Javier Elbio Irazoqui 2
Mehran Najibi 1 , Sid Ahmed Labed 1 , Orane Visvikis 1 , Javier Elbio Irazoqui 2

[No authors listed]

Author information
  • 1 Laboratory of Comparative Immunology, Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital Research Institute, Harvard Medical School, Boston, MA 02114, USA.
  • 2 Laboratory of Comparative Immunology, Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital Research Institute, Harvard Medical School, Boston, MA 02114, USA. Electronic address: jirazoqui@mgh.harvard.edu.

摘要


The mechanisms that tightly control the transcription of host defense genes have not been fully elucidated. We previously identified TFEB as a transcription factor important for host defense, but the mechanisms that regulate TFEB during infection remained unknown. Here, we used C. elegans to discover a pathway that activates TFEB during infection. Gene dkf-1, which encodes a homolog of protein kinase D (PKD), was required for TFEB activation in nematodes infected with Staphylococcus aureus. Conversely, pharmacological activation of PKD was sufficient to activate TFEB. Furthermore, phospholipase C (PLC) gene plc-1 was also required for TFEB activation, downstream of Gαq homolog egl-30 and upstream of dkf-1. Using reverse and chemical genetics, we discovered a similar PLC-PKD-TFEB axis in Salmonella-infected mouse macrophages. In addition, was required in macrophages. These observations reveal a previously unknown host defense signaling pathway, which has been conserved across one billion years of evolution.