Oxidized DJ-1 interacts with the mitochondrial protein BCL-XL |
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Authors: | Ren Haigang Fu Kai Wang Dan Mu Chenchen Wang Guanghui |
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Institution: | Laboratory of Molecular Neuropathology, Key Laboratory of Brain Functions and Diseases and School of Life Sciences, University of Science & Technology of China, Chinese Academy of Sciences, Hefei, Anhui 230027, People's Republic of China and. |
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Abstract: | 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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Keywords: | Mitochondria Parkinson''s Disease Protein Degradation Protein Stability Ubiquitination Bcl-XL DJ-1 |
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