Fas engagement induces neurite growth through ERK activation and p35 upregulation.

Nature Cell Biol. 5, 118-125, 2003.

Speaker: 吳怡靜                                                    Date: PM 2:00~3:00; 21/04/2004

Commentator: 黃阿敏  老師                              Place: Room 601

Abstract:

Fas (CD95) is a membrane protein belonging to the tumor-necrosis factor receptor (TNF) superfamily. Fas engagement by Fas ligand activates the caspase cascade that ultimately results in intracellular proteolysis and death (1). However, Fas not only mediates apoptosis but also stimulates proliferation, regeneration, and cytokine production in some circumstances. An alternative signaling pathway downstream of Fas in addition to caspases activation pathway involves the extracellular-signal regulated kinase (ERK) pathway (2), which plays a role in the cellular responses to many different growth and differentiation factors. In comparison of the well-characterized apoptotic pathway, the biological role of ERK activation downstream of Fas remains controversial. In this paper, the authors showed that crosslinking Fas on neurons activated the ERK/p35 pathway, but not apoptosis pathway. Fas engagement on neurite induced neurite outgrowth, which was dependent on ERK activation. Moreover, endogenous Fas expression accelerated functional recovery after nerve injury in mice. Therefore, the expression of Fas on neuron cells enhances neurite growth and accelerates recovery after nerve injury in the nervous system.

References:

1.      Nagata, S. Apoptosis by death factor. Cell, 88:355-365, 1997.

2.      Shinohara, H.,et al. Fas drives cell cycle progression in glioma cells via extracellular signal-regulated kinase. Cancer Res. 60, 1766-1772, 2000.