TY - JOUR
T1 - Hereditary spastic paraplegia protein spartin is an FK506-binding protein identified by mRNA display
AU - Tokunaga, Mayuko
AU - Shiheido, Hirokazu
AU - Hayakawa, Ichigo
AU - Utsumi, Akiko
AU - Takashima, Hideaki
AU - Doi, Nobuhide
AU - Horisawa, Kenichi
AU - Sakuma-Yonemura, Yuko
AU - Tabata, Noriko
AU - Yanagawa, Hiroshi
N1 - Funding Information:
We thank Drs. Seiji Tateyama and Toru Tsuji for experimental advice and useful discussions. This research was supported in part by the Program for Promotion of Fundamental Studies in Health Sciences of the NIBIO of Japan; a grant for the Core Research for Evolutionary Science and Technology of the Japan Science and Technology Agency; and a grant-in-aid for scientific research, a special coordination fund grant, and a Strategic Research Foundation Grant-aided Project for Private Universities (S0801008) from the MEXT of Japan.
PY - 2013/7/25
Y1 - 2013/7/25
N2 - Here, we used mRNA display to search for proteins that bind to FK506, a potent immunosuppressant drug, and identified spartin, a hereditary spastic paraplegia protein, from a human brain cDNA library. We demonstrated that FK506 binds to the C-terminal region of spartin and thereby inhibits the interaction of spartin with TIP47, one of the lipid droplet-associated proteins. We further confirmed that FK506 inhibits localization of spartin and its binder, an E3 ubiquitin ligase AIP4, in lipid droplets and increases the protein level of ADRP (adipose differentiation-related protein), which is a regulator of lipid homeostasis. These results strongly suggest that FK506 suppresses the proteasomal degradation of ADRP, a substrate of AIP4, by inhibiting the spartin-TIP47 interaction and thereby blocking the localization of spartin and AIP4 in lipid droplets.
AB - Here, we used mRNA display to search for proteins that bind to FK506, a potent immunosuppressant drug, and identified spartin, a hereditary spastic paraplegia protein, from a human brain cDNA library. We demonstrated that FK506 binds to the C-terminal region of spartin and thereby inhibits the interaction of spartin with TIP47, one of the lipid droplet-associated proteins. We further confirmed that FK506 inhibits localization of spartin and its binder, an E3 ubiquitin ligase AIP4, in lipid droplets and increases the protein level of ADRP (adipose differentiation-related protein), which is a regulator of lipid homeostasis. These results strongly suggest that FK506 suppresses the proteasomal degradation of ADRP, a substrate of AIP4, by inhibiting the spartin-TIP47 interaction and thereby blocking the localization of spartin and AIP4 in lipid droplets.
UR - http://www.scopus.com/inward/record.url?scp=84880887564&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84880887564&partnerID=8YFLogxK
U2 - 10.1016/j.chembiol.2013.05.011
DO - 10.1016/j.chembiol.2013.05.011
M3 - Article
C2 - 23890011
AN - SCOPUS:84880887564
SN - 1074-5521
VL - 20
SP - 935
EP - 942
JO - Chemistry and Biology
JF - Chemistry and Biology
IS - 7
ER -