title: Involvement of molecular chaperones in intracellular protein breakdown.
abstract: In all cells and organelles, there exist multiple molecular chaperones, which not only can facilitate the proper folding, transport and assembly of multimeric structures, but also appear to function in intracellular protein degradation. Recent findings in E. coli indicate that the major chaperones of the Hsp70 (DnaK) and Hsp60 (GroEL) families and their cofactors (DnaJ, GrpE or GroEL and Trigger Factor) associate with certain short-lived proteins (e.g. mutant polypeptides or regulatory proteins) and promote their degradation by the ATP-dependent proteases, La (lon or ClpP). Moreover, ATPases of ClpA/B family not only function in ATP-dependent proteolysis in association with the Clp protease, but by themselves can facilitate or act as chaperones in protein assembly. In eukaryotes, Hsp70 and their cofactors, the DnaJ homologs, are essential for the ubiquitination of certain abnormal and regulatory proteins and in the breakdown of certain polyubiquitinated polypeptides by 26S proteasome. It is likely that the chaperones function in proteolysis either as elements that faciliate the recognition of unfolded proteins or that the chaperones partially unfold substrates to make them more susceptible to proteases or ubiquitinating enzymes.
authors.affiliation: Boston Biomedical Research Institute, MA 02114, USA.
authors.forename: M Y
authors.initials: MY
authors.lastname: Sherman
authors.forename: A L
authors.initials: AL
authors.lastname: Goldberg
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D050956:HSP40 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D008954:Models, Biological; D018832:Molecular Chaperones / Q000378:metabolism*; D017510:Protein Folding; D011506:Proteins / Q000378:metabolism*; D014452:Ubiquitins / Q000378:metabolism
chemical_list: D050956:HSP40 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D011506:Proteins; D014452:Ubiquitins; D000255:Adenosine Triphosphate