Structural and biochemical investigation into human DJ-1 implicated in the pathogenesis of parkinson’s disease
Structure of dimeric DJ-1
DJ-1, which is extensively expressed in the testis and moderately in other tissues, was first identified as a novel candidate of the oncogene product that transformed mouse NIH3T3 cells in cooperation with activated ras. After the first identification, various physiological roles of DJ-1 have been unveiled. It has been shown that DJ-1 is a circulation tumor antigen in breast cancer, in which DJ-1 is secreted from cells to serum. DJ-1 was also characterized as a protein that regulates an RNA-protein interaction and positively modulates the androgen receptor (AR). Remarkably, the loss of function mutations in DJ-1 gene was revealed to be responsible for the autosomal recessive early-onset Parkinson’s disease (PD). Compatible with diverse cellular functions, human DJ-1 has at least three distinct biochemical activities: chaperon activity, protease activity, and glyoxalase activity.
Our research team reported for the first time the chaperon activity of human DJ-1 based on its structural similarity to an Escherichia coli chaperon, Hsp31. We also discovered that inorganic phosphate induces the filamentous aggregation of human DJ-1 and determined the high resolution crystal structure of the DJ-1 aggregates. Furthermore, through collaboration, we showed that DJ-1 binds to FGF receptor-1 and is implicated in osteogenesis and angeogenesis. Now we seek to unveil the pathological role of DJ-1 filamentous aggregates, to find out chemical agents preventing DJ-1 aggregation, and to solve the complex structure between DJ-1 and FGF receptor-1.
Namjoon Cho¶, Jaegeon Joo¶, Sunkyung Choi, Bu-Gyeong Kang, Andrew J.Lee, So-Yeon Youn, Su-Hyung Park, Eun-Mi Kim, Eliezer Masliah, Yuji Ko, Sun-Shin Cha*, Inkyung Jung*, Kee K.Kim*
"A novel splicing variant of DJ-1 in Parkinson's disease induces mitochondrial dysfunction"
Heliyon, Feb 26; https://doi.org/10.1016/j.heliyon.2023.e14039(2023)
Sanguk Yun*, Sun-Shin Cha and Jae Ho Kim*
"DJ-1 promotes cell migration by interacting with Mena, the mammalian homolog of Drosophila enabled"
Advances in Biological Regulation, Dec 16; https://doi.org/10.1016/j.jbior.2022.100943(2022)
Julee Kim, Sangki Baek, Yean Ju Hong, Michelle Novais de Paula, Musharrat Jahan Prima, Yeon-Mok Oh, Sun-Shin Cha, Jeong Tae Do, Yeon Jin Jang, Han Choe*
"DJ-1 can replace FGF-2 in defined media and feeder-free condition for long-term culture of human pluripotent stem cells"
International Journal of Molecular Sciences, May 29 accepted (2021)
Mi-Kyung Lee¶, Min-Sung Lee¶,Da-Woon Bae, Dong-Hwa Lee, Sun-Shin Cha*, Seung-Wook Chi*
"Structural characterization of interaction between DJ-1 and Bcl-XL using NMR spectroscopy"
Biochemical and Biophysical Research Communications, Jan 1; 495(1):1067-1073 (2018)
Min Soo Kim¶,Sangmin Lee¶,Sanguk Yun, Pann-Ghill Suh, Jongmi Park, Minghua Cui, Sun Choi, Sun-Shin Cha*, Wook Jin*
"Inhibitory effect of tartrate against phosphate-induced DJ-1 aggregation"
International Journal of Biological Macromolecules,Feb; 107(Pt B): 1650-1658 (2018)
Sun-Joo Lee, So Jung Kim, In-Kwon Kim, Junsang Ko, Chang-Sook Jeong, Gyung-Hwa Kim, Chankyu Park, Sa-Ouk Kang, Pann-Ghill Suh, Heung-Soo Lee, and Sun-Shin Cha*
"Crystal structures of human DJ-1 and Escherichia coli Hsp31 that share an evolutionarily conserved domain"
Journal of Biological ChemistryNov 7, 278, 44552-44559 (2003)
Sun-Shin Cha*, Ha Il Jung, Hyesung Jeon, Young Jun An, In-Kwon Kim, Sanguk Yun, Hyun Jin Ahn, Kwang Chul Chung, Sang Hee Lee, Pann-Ghill Suh, and Sa-Ouk Kang*
"Crystal structure of filamentous aggregates of human DJ-1 formed in an inorganic phosphate-dependent manner"
Journal of Biological Chemistry Dec 5;283(49):34069-34075 (2008)
Hai-Tuong Le, Valérie Gautier, Fatoum Kthiri,, Abderrahim Malki, Nadia Messaoudi, Mouadh Mihoub, Ahmed Landoulsi, Young Jun An, Sun-Shin Cha and Gilbert Richarme*
"YajL, the prokaryotic homolog of the Parkinsonism associated protein DJ-1, functions as a covalent chaperone for the thiol proteome"
Journal of Biological Chemistry Feb 17;287(8):5861-5870 (2012)
Hoi Jong Jung, Sangok Kim, Yun Jae Kim, Min-Kyu Kim, Sung Gyun Kang, Jung-Hyun Lee, Wankyu Kim*, and Sun-Shin Cha*
"Dissection of the dimerization modes in the DJ-1 superfamily"
Molecules and Cells Feb;33(2):163-171 (2012)
Jung-Min Kim, Hong-In Shin, Sun-Shin Cha, Chang Sup Lee, Bok Sil Hong, Seyoung Lim, Hyun-Jun Jang, Jaeyoon Kim, Yong Ryoul Yang, Yun-Hee Kim, Sanguk Yun, Girdhari Rijal, Whaseon Lee-Kwon, Jeong Kon Seo, Yong Song Gho, Sung Ho Ryu, Eun-Mi Hur, and Pann-Ghill Suh*
"DJ-1 promotes angiogenesis and osteogenesis by activating FGF receptor-1 signaling"
Nature CommunicationsDec 18;3:1296 (2012)