The proteasome activator PA28 functions in collaboration with Hsp90 in vivo.
We have previously shown that the proteasome activator PA28 is essential to Hsp90-dependent protein refolding in vitro, where PA28 mediates transfer of the Hsp90-bound substrate protein to the Hsc70/Hsp40 chaperone machine for its correct refolding. This observation suggests that PA28 may also collaborate with Hsp90 in cells. To examine this possibility, here we have used double-stranded RNA interference (RNAi) against PA28 in Caenorhabditis elegans mutants of daf-21, which encodes Hsp90. We show that C. elegans PA28 facilitates Hsp90-initiated protein refolding, albeit with an activity lower than that of mouse PA28 proteins. RNAi-mediated knockdown of PA28 significantly suppresses the Daf-c (dauer formation constitutive) phenotype of the daf-21 mutant, but it has no affect on the distinct defects of this mutant in sensing odorants. Taking these results together, we conclude that PA28 is likely to function in collaboration with Hsp90 in vivo.
Minami
Michiko
M
Department of Natural and Environmental Science, Faculty of Education, Tokyo Gakugei University, Koganei, Tokyo 184-8501, Japan.
Shinozaki
Fumika
F
Suzuki
Miho
M
Yoshimatsu
Katsuhiko
K
Ichikawa
Yoshimasa
Y
Minami
Yasufumi
Y
D000818:Animals; D017173:Caenorhabditis elegans / Q000033:anatomy & histology / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D018841:HSP90 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism*; D061988:Proteasome Inhibitors; D034622:RNA Interference; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism
D029742:Caenorhabditis elegans Proteins; C410905:DAF-12 protein, C elegans; C510188:DAF-21 protein, C elegans; D018841:HSP90 Heat-Shock Proteins; D061988:Proteasome Inhibitors; D018160:Receptors, Cytoplasmic and Nuclear; D046988:Proteasome Endopeptidase Complex