p62, Ref(2)P and ubiquitinated proteins are conserved markers of neuronal aging, aggregate formation and progressive autophagic defects

Abstract

(2011) p62, Ref(2)P and ubiquitinated proteins are conserved markers of neuronal aging, aggregate formation and progressive autophagic defects, Autophagy, 7:6, 572-583,

Lewy Body-like α-Synuclein Aggregates Resist Degradation and Impair Macroautophagy

“…4, A and B). Additionally, the levels of Triton X-100-insoluble HMW-Ub proteins, which are typically degraded by autophagy (43,44), were significantly increased in Pff-td HEK293 ␣-syn cells in the absence or presence of proteasome inhibition (data not shown) but not in Pff-td naive HEK293 cells (Fig. 4, C and D).…”

Nuclear Factor–Erythroid-2–Related Factor 2 in Aging and Lung Fibrosis

“…67 However, although age-dependent increases in p62 levels may occur, it has been reported to self-aggregate in aging, leading to decreased activity. 68 This represents one potential mechanism for the paradoxical impairment of Nrf2 signaling with aging.…”

p62/Sequestosome-1, Autophagy-related Gene 8, and Autophagy in Drosophila Are Regulated by Nuclear Factor Erythroid 2-related Factor 2 (NRF2), Independent of Transcription Factor TFEB

“…1A). It has not been tested whether Ref (2)P is able to bind directly to D. melanogaster Atg8, although Ref(2)P accumulates upon autophagy deficiency, suggesting that it may be a selective autophagy substrate (39,43,44). We first analyzed and showed binding of in vitro translated Ref (2)P to recombinant GST-DmAtg8a in a pull-down assay (Fig.…”

“…melanogaster ref (2)P is the orthologue of mammalian p62 (25,(37)(38)(39)(40) and was first characterized as a modifier of virus multiplication (38,41,42). Ref (2)P has been reported to be a major component of protein aggregates in flies defective in autophagy or with impaired proteasomal function and in fly models of neurodegenerative diseases (39,43,44). However, it is not known if Ref (2)P binds directly to DmAtg8 via a functional LIR motif.…”