Modulation of deregulated chaperone-mediated autophagy by a phosphopeptide
Christophe Macri, Fengjuan Wang, Inmaculada Tasset, Nicolas Schall, Nicolas Page, Jean-Paul Briand, Ana Maria Cuervo, Sylviane Muller
AUTOPHAGY | TAYLOR & FRANCIS INC | Published : 2015
The P140 peptide, a 21-mer linear peptide (sequence 131-151) generated from the spliceosomal SNRNP70/U1-70K protein, contains a phosphoserine residue at position 140. It significantly ameliorates clinical manifestations in autoimmune patients with systemic lupus erythematosus and enhances survival in MRL/lpr lupus-prone mice. Previous studies showed that after P140 treatment, there is an accumulation of autophagy markers sequestosome 1/p62 and MAP1LC3-II in MRL/lpr B cells, consistent with a downregulation of autophagic flux. We now identify chaperone-mediated autophagy (CMA) as a target of P140 and demonstrate that its inhibitory effect on CMA is likely tied to its ability to alter the comp..View full abstract
Awarded by NATIONAL INSTITUTE ON AGING
This research was funded by the French Center National de la Recherche Scientifique and the Laboratory of Excellence Medalis, Initiative of Excellence (IdEx), Strasbourg University and the National Institute on Aging of the National Institute of Health. CM was supported by a Region Alsace and ImmuPharma France doctoral fellowship. FW was supported by a post-doctoral grant from the University of Strasbourg Institute for Advanced Study (USIAS). IT was supported by a Fulbright fellowship from the Ministerio de Educacion y Ciencia.