Protein Research
Laboratory

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.

[Related publications]

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;9(3):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, May:88:100943 (2023)

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 31;22(11):5954 (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-X_L 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)