TY  - JOUR
AU  - Zaffagnini, G.
AU  - Savova, A.
AU  - Danieli, A.
AU  - Romanov, J.
AU  - Tremel, S.
AU  - Ebner, M.
AU  - Peterbauer, T.
AU  - Sztacho, M.
AU  - Trapannone, R.
AU  - Tarafder, A. K.
AU  - Sachse, Carsten
AU  - Martens, S.
TI  - Phasing out the bad-How SQSTM1/p62 sequesters ubiquitinated proteins for degradation by autophagy
JO  - Autophagy
VL  - 14
IS  - 7
SN  - 1554-8627
CY  - Abingdon, Oxon
PB  - Taylor & Francis
M1  - FZJ-2018-05901
SP  - 1280-1282
PY  - 2018
AB  - The degradation of misfolded, ubiquitinated proteins is essential for cellular homeostasis. These proteins are primarily degraded by the ubiquitin-proteasome system (UPS) and macroautophagy/autophagy serves as a backup mechanism when the UPS is overloaded. How autophagy and the UPS are coordinated is not fully understood. During the autophagy of misfolded, ubiquitinated proteins, referred to as aggrephagy, substrate proteins are clustered into larger structures in a SQSTM1/p62-dependent manner before they are sequestered by phagophores, the precursors to autophagosomes. We have recently shown that SQSTM1/p62 and ubiquitinated proteins spontaneously phase separate into micrometer-sized clusters in vitro. This enabled us to characterize the properties of the ubiquitin-positive substrates that are necessary for the SQSTM1/p62-mediated cluster formation. Our results suggest that aggrephagy is triggered by the accumulation of substrates with multiple ubiquitin chains and that the process can be inhibited by active proteasomes.
LB  - PUB:(DE-HGF)16
C6  - pmid:29929426
UR  - <Go to ISI:>//WOS:000441624100020
DO  - DOI:10.1080/15548627.2018.1462079
UR  - https://juser.fz-juelich.de/record/856514
ER  -