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A switch from BAG1 to BAG3 during ageing triggers the enhanced use of the autophagic‐lysosomal system for the degradation of polyubiquitinated proteins
Author(s) -
Gamerdinger Martin,
Hajieva Parvana,
Behl Christian
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.668.1
Subject(s) - bag3 , autophagy , microbiology and biotechnology , biology , biochemistry , apoptosis
BAG1 and BAG3 are members of the Bcl‐2‐associated athanogene (BAG) family, a conserved group of Hsp70 co‐regulators. We show that both, BAG1 and BAG3, are involved in protein quality control: whereas BAG1 regulates the removal of polyubiquitinated proteins by the proteasomal system, BAG3 acts in concert with the ubiquitin‐binding protein p62/SQSTM1 to stimulate the turnover of polyubiquitinated proteins by the autophagic‐lysosomal pathway. Interestingly, a switch from BAG1 to BAG3 occurs during ageing of human cells as well as in neurons of the aged rodent brain. Similar to the ageing models, a shift from BAG1 to BAG3 is observed in HEK cells under protein cross‐linking conditions provoked by oxidative stress. Moreover, we show that, triggered by the increased BAG3 to BAG1 ratio, aged cells use increasingly the autophagic‐lysosomal pathway for the turnover of polyubiquitinated proteins. We conclude that the BAG3‐mediated recruitment of the autophagy pathway is an important adaptation of the cellular protein quality control system to maintain protein homeostasis in the presence of an enhanced pro‐oxidant and aggregation‐prone milieu characteristic of ageing. This work was supported by grants from the Fritz und Hildegard Berg‐Stiftung