Proper SUMO-1 conjugation is essential to DJ-1 to exert its full activities.
DJ-1 is a multifunctional protein that plays roles in transcriptional regulation and antioxidative stress, and loss of its function is thought to result in the onset of Parkinson's disease (PD). Here, we report that DJ-1 was sumoylated on a lysine residue at amino-acid number 130 (K130) by PIASxalpha or PIASy. The K130 mutation abrogated all of the functions of DJ-1, including ras-dependent transformation, cell growth promotion and anti-UV-induced apoptosis activities. Sumoylation of DJ-1 was increased after UV irradiation concomitant with a pI shift to an acidic point of DJ-1. Furthermore, L166P, a mutant DJ-1 found in PD patients, and K130RX, an artificial mutant containing four mutations in DJ-1, were improperly sumoylated, and they became insoluble, partly localized in the mitochondria and degraded by the proteasome system. Both L166P-expressing cells and DJ-1-knockdown cells were found to be highly susceptible to UV-induced cell apoptosis.
Shinbo
Y
Y
Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
Niki
T
T
Taira
T
T
Ooe
H
H
Takahashi-Niki
K
K
Maita
C
C
Seino
C
C
Iguchi-Ariga
S M M
SM
Ariga
H
H
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D002460:Cell Line; D004247:DNA / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008239:Lysine / Q000737:chemistry; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D015513:Oncogene Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010300:Parkinson Disease / Q000235:genetics / Q000378:metabolism; D000071617:Protein Deglycase DJ-1; D051381:Rats; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D025842:SUMO-1 Protein / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D012995:Solubility; D014162:Transfection; D014466:Ultraviolet Rays
D047908:Intracellular Signaling Peptides and Proteins; D015513:Oncogene Proteins; D011994:Recombinant Proteins; D025842:SUMO-1 Protein; D004247:DNA; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1; D008239:Lysine