TY - JOUR
T1 - Oxidized DJ-1 interacts with the mitochondrial protein BCL-X L
AU - Ren, Haigang
AU - Fu, Kai
AU - Wang, Dan
AU - Mu, Chenchen
AU - Wang, Guanghui
PY - 2011/10/7
Y1 - 2011/10/7
N2 - Parkinson disease (PD)- and cancer-associated protein, DJ-1, mediates cellular protection via many signaling pathways. Deletions or mutations in the DJ-1 gene are directly linked to autosomal recessive early-onset PD. DJ-1 has potential roles in mitochondria. Here, we show that DJ-1 increases its mitochondrial distribution in response to ultraviolet B (UVB) irradiation and binds to Bcl-X L. The interactions between DJ-1 and Bcl-X L are oxidation-dependent. DJ-1(C106A), a mutant form of DJ-1 that is unable to be oxidized, binds Bcl-X L much less than DJ-1 does. Moreover, DJ-1 stabilizes Bcl-X L protein level by inhibiting its ubiquitination and degradation through ubiquitin proteasome system (UPS) in response to UVB irradiation. Furthermore, under UVB irradiation, knockdown of DJ-1 leads to increases of Bcl-X L ubiquitination and degradation upon UVB irradiation, thereby increasing mitochondrial Bax, caspase-3 activation and PARP cleavage. These data suggest that DJ-1 protects cells against UVB-induced cell death dependent on its oxidation and its association with mitochondrial Bcl-X L.
AB - Parkinson disease (PD)- and cancer-associated protein, DJ-1, mediates cellular protection via many signaling pathways. Deletions or mutations in the DJ-1 gene are directly linked to autosomal recessive early-onset PD. DJ-1 has potential roles in mitochondria. Here, we show that DJ-1 increases its mitochondrial distribution in response to ultraviolet B (UVB) irradiation and binds to Bcl-X L. The interactions between DJ-1 and Bcl-X L are oxidation-dependent. DJ-1(C106A), a mutant form of DJ-1 that is unable to be oxidized, binds Bcl-X L much less than DJ-1 does. Moreover, DJ-1 stabilizes Bcl-X L protein level by inhibiting its ubiquitination and degradation through ubiquitin proteasome system (UPS) in response to UVB irradiation. Furthermore, under UVB irradiation, knockdown of DJ-1 leads to increases of Bcl-X L ubiquitination and degradation upon UVB irradiation, thereby increasing mitochondrial Bax, caspase-3 activation and PARP cleavage. These data suggest that DJ-1 protects cells against UVB-induced cell death dependent on its oxidation and its association with mitochondrial Bcl-X L.
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U2 - 10.1074/jbc.M110.207134
DO - 10.1074/jbc.M110.207134
M3 - Article
C2 - 21852238
AN - SCOPUS:80053399227
SN - 0021-9258
VL - 286
SP - 35308
EP - 35317
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 40
ER -