TY  - JOUR
A1  - Domínguez Bautista, Jorge Antolio
A1  - Klinkenberg, Michael
A1  - Brehm, Nadine
A1  - Subramaniam, Mahalakshmi
A1  - Kern, Beatrice
A1  - Roeper, Jochen
A1  - Auburger, Georg
A1  - Jendrach, Marina
T1  - Loss of lysosome-associated membrane protein 3 (LAMP3) enhances cellular vulnerability against proteasomal inhibition
T2  - European journal of cell biology
N2  - The family of lysosome-associated membrane proteins (LAMP) includes the ubiquitously expressed LAMP1 and LAMP2, which account for half of the proteins in the lysosomal membrane. Another member of the LAMP family is LAMP3, which is expressed only in certain cell types and differentiation stages. LAMP3 expression is linked with poor prognosis of certain cancers, and the locus where it is encoded was identified as a risk factor for Parkinson's disease (PD). Here, we investigated the role of LAMP3 in the two main cellular degradation pathways, the proteasome and autophagy. LAMP3 mRNA was not detected in mouse models of PD or in the brain of human patients. However, it was strongly induced upon proteasomal inhibition in the neuroblastoma cell line SH-SY5Y. Induction of LAMP3 mRNA following proteasomal inhibition was dependent on UPR transcription factor ATF4 signaling and induced autophagic flux. Prevention of LAMP3 induction enhanced apoptotic cell death. In summary, these data demonstrate that LAMP3 regulation as part of the UPR contributes to protein degradation and cell survival during proteasomal dysfunction. This link between autophagy and the proteasome may be of special importance for the treatment of tumor cells with proteasomal inhibitors.
KW  - Autophagy
KW  - Cancer
KW  - LAMP3
KW  - Lysosome
KW  - Parkinson's disease
KW  - Proteasome
Y1  - 2015
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/36629
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-366292
SN  - 1618-1298
SN  - 0171-9335
N1  - © 2015 The Authors. Published by Elsevier GmbH. This is an open access article under the CCBY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
VL  - 94
IS  - 3-4
SP  - 148
EP  - 161
PB  - Elsevier
CY  - Amsterdam ; Boston, Mass. ; London ; New York, NY ; Oxford ; Paris ; Philadelphia, Pa. ; San Diego, Ca. ; St. Louis, Mo. ; München
ER  -