HSPA8 acts as an amyloidase to suppress necroptosis by inhibiting and reversing functional amyloid formation.

ABSTRACT: Ultra-stable fibrous structure is a hallmark of amyloids. In contrast to canonical disease-related amyloids, emerging research indicates that a significant number of cellular amyloids, termed 'functional amyloids', contribute to signal transduction as temporal signaling hubs in humans. However, it is unclear how these functional amyloids are effectively disassembled to terminate signal transduction. RHIM motif-containing amyloids, the largest functional amyloid family discovered thus far, play an important role in mediating necroptosis signal transduction in mammalian cells. Here, we identify heat shock protein family A member 8 (HSPA8) as a new type of enzyme - which we name as 'amyloidase' - that directly disassembles RHIM-amyloids to inhibit necroptosis signaling in cells and mice. Diff

SUBMITTER: Wu E 

PROVIDER: S-EPMC10624691 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature