FGF21 Induced by the ASK1-p38 Pathway Promotes Mechanical Cell Competition by Attracting Cells.

Cell competition is a social cellular phenomenon in which unfit cells are selectively eliminated to maintain tissue homeostasis. Recent studies have revealed that mechanical forces induce competitive cell-cell interactions in Drosophila. This mechanical cell competition has also been reported to play an important role in mammalian cells, using Madin-Darby canine kidney (MDCK) cells depleted of a polarity regulator Scribble in a tetracycline-inducible manner (scrib cells).

Apoptosis signal-regulating kinase 1 as a therapeutic target.

Introduction: All organisms are ordinarily exposed to various stresses. It is important for organisms to possess appropriate stress response mechanisms and to maintain homeostasis because the disruption of a stress response system can cause various diseases. Apoptosis signal-regulating kinase 1 (ASK1) is one of the stress-responsive MAP3Ks.

Roquin-2 promotes ubiquitin-mediated degradation of ASK1 to regulate stress responses.

Apoptosis signal-regulating kinase 1 (ASK1, also known as MAP3K5) mediates reactive oxygen species (ROS)-induced cell death. When activated by ROS, ASK1 ultimately becomes ubiquitinated and degraded by the proteasome, a process that is antagonized by the ubiquitin-specific protease USP9X. Using a functional siRNA (small interfering RNA) screen in HeLa cells, we identified Roquin-2 (also called RC3H2) as an E3 ubiquitin ligase required for ROS-induced ubiquitination and degradation of ASK1.