Proteasome-dependent degradation of cytosolic chaperonin CCT.
The chaperonin containing t-complex polypeptide 1 (CCT) is a heterooligomeric molecular chaperone that assists in the folding of actin, tubulin, and other cytosolic proteins. We show here that degradation of CCT in mammalian cells is inhibited by a proteasome-specific inhibitor, lactacystin. When CCT synthesis was inhibited by growth arrest of cells, the decrease in CCT levels was much slower in the presence of lactacystin than in its absence. Pulse-chase experiments indicated that degradation of CCT is inhibited 2- to 2.5-fold by addition of lactacystin. In addition, CCT degradation rate in ts85 cells that produce thermolabile ubiquitin-activating enzyme E1 was reduced 3-fold at the nonpermissive temperature compared to the degradation at the permissive temperature. These results indicate that the ubiquitin-proteasome system is involved in CCT degradation.
Yokota
S
S
HSP Research Institute, Kyoto Research Park, Kyoto, 600-8813, Japan.
Kayano
T
T
Ohta
T
T
Kurimoto
M
M
Yanagi
H
H
Yura
T
T
Kubota
H
H
D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D002455:Cell Division; D056404:Chaperonin Containing TCP-1; D018833:Chaperonins / Q000378:metabolism*; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism; D004795:Enzyme Stability; D005260:Female; D007700:Kinetics; D008025:Ligases / Q000378:metabolism; D008325:Mammary Neoplasms, Experimental; D051379:Mice; D009097:Multienzyme Complexes / Q000378:metabolism*; D009101:Multiple Myeloma; D011480:Protease Inhibitors / Q000494:pharmacology; D046988:Proteasome Endopeptidase Complex; D013696:Temperature; D013816:Thermodynamics; D014407:Tumor Cells, Cultured; D044764:Ubiquitin-Activating Enzymes; D044767:Ubiquitin-Protein Ligases
D015853:Cysteine Proteinase Inhibitors; D009097:Multienzyme Complexes; D011480:Protease Inhibitors; C533315:Tcp1 protein, mouse; C067713:lactacystin; D044767:Ubiquitin-Protein Ligases; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; D000251:Adenosine Triphosphatases; D056404:Chaperonin Containing TCP-1; D018833:Chaperonins; D008025:Ligases; D044764:Ubiquitin-Activating Enzymes; D000111:Acetylcysteine