FAM48A mediates compensatory autophagy induced by proteasome impairment

Abstract

Maintaining protein homeostasis is central to cell survival. The ubiquitin-proteasome system and autophagy play pivotal roles in protein quality control through protein degradation. Activities of these degradative pathways are carefully orchestrated, and autophagy is up-regulated during proteasome dysfunction for cellular homeostasis. However, the mechanism by which proteasome impairment induces compensatory autophagy has remained largely elusive. Here, we show that FAM48A mediates autophagy induction during proteasome inhibition. FAM48A is degraded by the proteasome and accumulates in cells by proteasome inhibition. Knockdown of FAM48A led to defective induction of autophagy during proteasome inhibition and accompanied by defective localization of Atg9 on recycling endosomes. Our results indicate that FAM48A is a kind of sensor that is required for compensatory autophagy induction upon proteasome impairment. K E Y W O R D S autophagy, proteasome 560 | Genes to Cells ARATA eT Al.

The promiscuity of the SAGA complex subunits: Multifunctional or moonlighting proteins?

“…More recently, p38IP/hSpt20 was also associated with another type of autophagy, known as compensatory autophagy, which is induced after proteasome dysfunction. In this type of autophagy, p38IP, also known as FAM48A [67], accumulates in cells when the proteasome is inhibited and drives the correct localization of Atg9 into recycling endosomes, which is required for the compensatory autophagy that is induced upon proteasome impairment [67]. These combined studies demonstrated that p38IP/hSpt20/FAM48A can bind to proteins other than those in the SAGA complex and can act in cellular processes distinct from transcription.…”