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.
journal_name
Proc Natl Acad Sci U S Aauthors
Kim PK,Hailey DW,Mullen RT,Lippincott-Schwartz Jdoi
10.1073/pnas.0810611105subject
Has Abstractpub_date
2008-12-30 00:00:00pages
20567-74issue
52eissn
0027-8424issn
1091-6490pii
0810611105journal_volume
105pub_type
杂志文章abstract::The role of the products of the K and D loci of the H-2 complex as target antigens for cytotoxic T cells generated to modified syngeneic cells has been investigated. Spleen cells, when cocultured with trinitrophenyl-derivatized syngeneic cells, generate cytolytic T cells that lyse most effectively tumor or spleen targ...
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