TY - JOUR
T1 - CHIP is associated with Parkin, a gene responsible for familial Parkinson's Disease, and enhances its ubiquitin ligase activity
AU - Imai, Yuzuru
AU - Soda, Mariko
AU - Hatakeyama, Shigetsugu
AU - Akagi, Takumi
AU - Hashikawa, Tsutomu
AU - Nakayama, Kei Ichi
AU - Takahashi, Ryosuke
N1 - Funding Information:
We would like to thank K. Takio, H. Nakayama, and R. Araya for their assistance in the mass spectrometry analysis. This work was funded by research grants from RIKEN BSI, a Grant-in-Aid for Scientific Research on Priority Areas from the Ministry of Education, Culture, Sports, Science, and Technology, Japan, a Grant-in-Aid for Encouragement of Young Scientists from the Japan Society for the Promotion of Science, as well as grants from the Ministry of Health, Labor, and Welfare, Japan.
PY - 2002
Y1 - 2002
N2 - Unfolded Pael receptor (Pael-R) is a substrate of the E3 ubiquitin ligase Parkin. Accumulation of Pael-R in the endoplasmic reticulum (ER) of dopaminergic neurons induces ER stress leading to neurodegeneration. Here, we show that CHIP, Hsp70, Parkin, and Pael-R formed a complex in vitro and in vivo. The amount of CHIP in the complex was increased during ER stress. CHIP promoted the dissociation of Hsp70 from Parkin and Pael-R, thus facilitating Parkin-mediated Pael-R ubiquitination. Moreover, CHIP enhanced Parkin-mediated in vitro ubiquitination of Pael-R in the absence of Hsp70. Furthermore, CHIP enhanced the ability of Parkin to inhibit cell death induced by Pael-R. Taken together, these results indicate that CHIP is a mammalian E4-like molecule that positively regulates Parkin E3 activity.
AB - Unfolded Pael receptor (Pael-R) is a substrate of the E3 ubiquitin ligase Parkin. Accumulation of Pael-R in the endoplasmic reticulum (ER) of dopaminergic neurons induces ER stress leading to neurodegeneration. Here, we show that CHIP, Hsp70, Parkin, and Pael-R formed a complex in vitro and in vivo. The amount of CHIP in the complex was increased during ER stress. CHIP promoted the dissociation of Hsp70 from Parkin and Pael-R, thus facilitating Parkin-mediated Pael-R ubiquitination. Moreover, CHIP enhanced Parkin-mediated in vitro ubiquitination of Pael-R in the absence of Hsp70. Furthermore, CHIP enhanced the ability of Parkin to inhibit cell death induced by Pael-R. Taken together, these results indicate that CHIP is a mammalian E4-like molecule that positively regulates Parkin E3 activity.
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U2 - 10.1016/S1097-2765(02)00583-X
DO - 10.1016/S1097-2765(02)00583-X
M3 - Article
C2 - 12150907
AN - SCOPUS:0036345454
SN - 1097-2765
VL - 10
SP - 55
EP - 67
JO - Molecular Cell
JF - Molecular Cell
IS - 1
ER -