Abstract
The selective targeting and disposal of solid protein aggregates are essential for cells to maintain protein homoeostasis. Autophagy receptors including p62, NBR1, Cue5/TOLLIP (CUET), and Tax1-binding protein 1 (TAX1BP1) proteins function in selective autophagy by targeting ubiquitinated aggregates through ubiquitin-binding domains. Here, we summarize previous beliefs and recent findings on selective receptors in aggregate autophagy. Since there are many reviews on selective autophagy receptors, we focus on their oligomerization, which enables receptors to function as pathway determinants and promotes phase separation.
Highlights
Protein misfolding and the subsequent aggregation caused by various stressors can be cytotoxic to cells and may lead to cell death
Soluble substrates are mainly degraded through the proteasome pathway; tightly folded protein aggregates, are unable to traverse the narrow opening of the proteasome and are resistant to proteasomal degradation and may accumulate in cells as ubiquitinated species [4,5]
Conjugation of Atg8 to phagophores is essential for its expansion and is important for its function as a platform for the recruitment of its cargo, which is mediated by autophagy receptors [70,71,72,73]
Summary
Protein misfolding and the subsequent aggregation caused by various stressors can be cytotoxic to cells and may lead to cell death. Protein substrates with different statuses, soluble or aggregated, are targeted and degraded by proteasome and autophagy pathways, respectively [3]. Soluble and aggregated substrates are both modified with polyubiquitin chains, which were initially thought to form only on proteasomal substrates [6,7,8]. This common modification of different substrates generates a puzzle regarding how this degradation decision is made, especially considering that both pathways utilize ubiquitin-binding proteins as substrate receptors. We describe key features for these receptors to function in discriminating cargo aggregates from soluble proteins
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