Polyglutamined expanded androgen receptor interacts with chaperonin CCT.
CCT chaperonin is a highly conserved molecular chaperone, which plays an important role in the folding of complex proteins in mammalian cells. CCT chaperonin interacts with huntingtin and results in decrease of aggregate formation followed by increase of cell survival. Using yeast-two-hybrid system, we screen for specific CCT chaperonin subunit, which can recognize and bind to androgen receptor. We show that subunit 6 of CCT chaperonin interacts with androgen receptor. Interestingly, CCT chaperonin shows higher binding affinity to polyglutamine expanded androgen receptor than that of the wild-type. We prove this interaction in mammalian cell models, which show co-localization of androgen receptor and subunit 6 of CCT in cellular cytosol. Therefore, not only huntingtin but also androgen receptor is a polyglutamine expanded protein, which is a substrate of CCT chaperonin. Our results suggest that CCT might play an essential role in modulation of folding of polyglutamine expanded proteins and could be another target for further therapeutic studies.
Division of Molecular Genetics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Suttikarn
S
Pongtepaditep
Thawornchai
T
Limjindaporn
Patcharee
P
Lertrit
Chatchawan
C
Srisawat
Chanin
C
Limwongse
D000328:Adult; D056404:Chaperonin Containing TCP-1 / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D000071058:Huntingtin Protein; D008297:Male; D020966:Muscular Disorders, Atrophic / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D011944:Receptors, Androgen / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020798:Two-Hybrid System Techniques
C410798:AR protein, human; C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D010455:Peptides; D011944:Receptors, Androgen; C097188:polyglutamine; D056404:Chaperonin Containing TCP-1