Loss of lysosome-associated membrane protein 3 (LAMP3) enhances cellular vulnerability against proteasomal inhibition

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
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.
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Author:Jorge Antolio Domínguez Bautista, Michael Klinkenberg, Nadine Brehm, Mahalakshmi Subramaniam, Beatrice Kern, Jochen Roeper, Georg Auburger, Marina Jendrach
URN:urn:nbn:de:hebis:30:3-366292
DOI:http://dx.doi.org/10.1016/j.ejcb.2015.01.003
ISSN:1618-1298
ISSN:0171-9335
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=25681212
Parent Title (English):European journal of cell biology
Publisher:Elsevier
Place of publication:Amsterdam ; Boston, Mass. ; London ; New York, NY ; Oxford ; Paris ; Philadelphia, Pa. ; San Diego, Ca. ; St. Louis, Mo. ; München
Document Type:Article
Language:English
Date of Publication (online):2015/01/30
Date of first Publication:2015/01/30
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2015/04/29
Tag:Autophagy; Cancer; LAMP3; Lysosome; Parkinson's disease; Proteasome
Volume:94
Issue:3-4
Pagenumber:14
First Page:148
Last Page:161
Note:
© 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/).
HeBIS PPN:368952568
Institutes:Medizin
Dewey Decimal Classification:570 Biowissenschaften; Biologie
610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Sondersammelgebiets-Volltexte
Licence (German):License LogoCreative Commons - Namensnennung-Nicht kommerziell - Keine Bearbeitung 4.0

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