The Role of TAK1 in Yop J-induced Cell Death

Undergraduate #99
Discipline: Biological Sciences
Subcategory: Microbiology/Immunology/Virology

Alexandria Brooks - Alabama State University
Co-Author(s): Kristian Starheim and Egil Lien, University of Massachusetts Medical School, Worcester, MA

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Yersinia Pestis (Yp) is a Gram-negative bacterium that is the causative agent of plague. This bacterium’s ability to evade the host’s innate immune system gives it a high virulence. Yp secretes multiple proteins, Yops, into the host immune cells. YopJ causes cell death in a RIPK1-dependent manner. RIPK1 activates a system of innate immune response pathways such as the proinflammatory NF-B pathway, Caspase-8 dependent apoptosis, IL-1b release and RIP3 dependent necroptosis. An important proinflammatory kinase downstream of RIPK1 is TAK1. It leads to activation of NF-κB and AP-1-dependent transcription of proinflammatory genes. We hypothesized that TAK1 can partake in a Yp-induced switch from NF-B activation to cell death in concert with other factors in the RIPK1/NF-B/ MAPK pathway. We show that ∆YopJ infection combined with TAK1-inhibition phenocopies YopJ-induced cell death in macrophages, indicating that TAK1 is a central factor in YopJinduced cell death and immune regulation.

Funder Acknowledgement(s): NIH

Faculty Advisor: Egil Lien,