Abstract
Proteasome inhibition (PSMI) is known to activate macroautophagy (autophagy hereafter), but the underlying mechanisms remain to be fully delineated. Here we discuss our recent work identifying an important PPP3/calcineurin-TFEB-SQSTM1/p62 pathway in mediating activation of autophagy by PSMI, a compensatory process for the heart with proteasome malfunction. Through increasing PPP3/calcineurin activity and inhibiting MTOR signaling, PSMI promotes the dephosphorylation and thereby nuclear translocation of TFEB, resulting in transactivation of genes in the autophagic-lysosomal pathway (ALP) such as Mcoln1 and Sqstm1. We have discovered that SQSTM1 is required for not only induction of autophagy but also cardiac activation of TFEB by PSMI, unveiling a novel feedforward role for SQSTM1 in TFEB activation.
Original language | English (US) |
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Pages (from-to) | 2114-2116 |
Number of pages | 3 |
Journal | Autophagy |
Volume | 16 |
Issue number | 11 |
DOIs | |
State | Published - Nov 1 2020 |
Keywords
- PPP3/calcineurin
- PSMC2
- SQSTM1/p62
- TFEB
- macroautophagy
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology