Secretion was then stimulated by a synthetic small-molecule drug that induces protein disaggregation.
The Hsp100-mediated protein disaggregation is linked to the activity of other chaperones from the Hsp70 and Hsp40 families.
How protein disaggregation is achieved and whether survival is solely dependent on ClpB-mediated elimination of aggregates or also on reactivation of aggregated proteins has been unclear.
Protein disaggregation by the BAP/ClpP complex remains dependent on DnaK, defining a role for DnaK at early stages of the disaggregation reaction.
This review describes the current mechanistic model of the chaperone-induced protein disaggregation and explains how the structural architecture of Hsp100 supports disaggregation and how the co-chaperones may participate in the Hsp100-mediated reactions.
HSPA2 belongs to the large group of the heat shock protein 70 family, members of which generally function as molecular chaperones to stabilize the folded state of proteins, and control protein disaggregation [46].
Hypertonic shock provokes a rapid inhibition of protein synthesis, disaggregation of polysomes, dephosphorylation of eIF4E, 4E-BP1, S6 and an increased association of eIF4E and 4E-BP1 [ 11, 13].
Three different proteins promote the disaggregation of protein aggregates in yeast: Hsp104 and two members of the Hsp110 family, called Sse1 and Sse2 (Glover and Lindquist, 1998; Shorter, 2011; Duennwald et al., 2012; Rampelt et al., 2012; Doyle et al., 2013).
Molecular chaperones have central roles in each of the arms of the PN (protein synthesis, folding, disaggregation, and degradation), leading to the proposal that modulation of chaperone function could have therapeutic benefits for the large and growing family of diseases of protein conformation including neurodegeneration, metabolic diseases, and cancer.
The MoxR family is a subset of AAA + ATPases, a large, diverse group of ATPases associated with various cellular activities including cell-cycle regulation, DNA repair and replication, protein proteolysis and disaggregation, and so on.
These survival proteins have a broad range of functions, including molecular chaperones to assist with protein folding and disaggregation (Hendrick and Hartl 1993), cell wall remodeling (Imazu and Sakurai 2005), ubiquitin-related protein degradation, DNA- and RNA-modifying enzymes, metabolic enzymes, regulatory proteins, and others involved with maintenance of cell structure (Richter et al. 2010).
