Eukaryotic cells use autophagy and the ubiquitin–proteasome system as their major protein degradation pathways. Upon proteasomal impairment, cells switch to autophagy to ensure proper clearance of clients (the proteasome-to-autophagy switch). How the proteasomal clients are re-routed to the autophagosomal pathway has remained unclear. We found that several stress pathways that are induced upon disturbances in protein homeostasis as well as by direct chemically-induced proteasomal inhibition increase the protein levels of BAG3, a partner of the heat shock proteins HSPB8 and Hsp70. BAG3 induces the sequestration of Hsp70-bound proteasomal clients into cytoplasmic puncta which leads to their re-routing to autophagosomes for degradation. This occurs through competitive inhibition with its family member BAG1, which normally directs Hsp70-bound clients to the proteasome.

BAG3-mediated re-routing of protein degradation towards autophagy upon proteasomal impairment / Minoia, Melania; Boncoraglio, Alessandra; Vinet, Jonathan; Brunsting, Jeanette F.; Poletti, Angelo; Krom, Sabine; Reits, Eric; Kampinga, Harm H.; Carra, Serena. - (2013). ((Intervento presentato al convegno The biology of molecular chaperones: From molecules, organelles and cells to misfolding diseases. tenutosi a Santa Margherita di Pula, Italy nel 17-22 Maggio 2013.

BAG3-mediated re-routing of protein degradation towards autophagy upon proteasomal impairment

VINET, JONATHAN;CARRA, Serena
2013

Abstract

Eukaryotic cells use autophagy and the ubiquitin–proteasome system as their major protein degradation pathways. Upon proteasomal impairment, cells switch to autophagy to ensure proper clearance of clients (the proteasome-to-autophagy switch). How the proteasomal clients are re-routed to the autophagosomal pathway has remained unclear. We found that several stress pathways that are induced upon disturbances in protein homeostasis as well as by direct chemically-induced proteasomal inhibition increase the protein levels of BAG3, a partner of the heat shock proteins HSPB8 and Hsp70. BAG3 induces the sequestration of Hsp70-bound proteasomal clients into cytoplasmic puncta which leads to their re-routing to autophagosomes for degradation. This occurs through competitive inhibition with its family member BAG1, which normally directs Hsp70-bound clients to the proteasome.
The biology of molecular chaperones: From molecules, organelles and cells to misfolding diseases.
Santa Margherita di Pula, Italy
17-22 Maggio 2013
Minoia, Melania; Boncoraglio, Alessandra; Vinet, Jonathan; Brunsting, Jeanette F.; Poletti, Angelo; Krom, Sabine; Reits, Eric; Kampinga, Harm H.; Carra, Serena
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11380/1063166
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