Ubiquitin signals autophagic degradation of cytosolic proteins and peroxisomes.

Abstract:

:Autophagy is responsible for nonspecific, bulk degradation of cytoplasmic components. Recent work has revealed also that there is specific, autophagic degradation of polyubiquitinated protein aggregates, whose buildup occurs during neurodegenerative disease. Here, we report that simple mono-ubiquitination of normally long-lived cytoplasmic substrates is sufficient to target these substrates for autophagic degradation in mammalian cells. That is, upon their ubiquitination, both small [i.e., red fluorescent protein (RFP)] and large (i.e., peroxisomes) substrates are efficiently targeted to autophagosomes and then degraded within lysosomes upon autophagosome-lysosome fusion. This targeting requires the ubiquitin-binding protein, p62, and is blocked by the Class III phosphatidylinositol 3-kinase (PI3K) inhibitor, 3-methyladenine (3-MA), or by depletion of the autophagy-related-12 (Atg12) protein homolog. Mammalian cells thus use a common pathway involving ubiquitin and p62 for targeting diverse types of substrates for autophagy.

authors

Kim PK,Hailey DW,Mullen RT,Lippincott-Schwartz J

doi

10.1073/pnas.0810611105

subject

Has Abstract

pub_date

2008-12-30 00:00:00

pages

20567-74

issue

52

eissn

0027-8424

issn

1091-6490

pii

0810611105

journal_volume

105

pub_type

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