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.
J Biol Chem. 2011 Oct 7;286(40):35308-17. doi: 10.1074/jbc.M110.207134. Epub 2011 Aug 18.
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).
帕金森病（PD）和癌症相关蛋白 DJ-1 通过多种信号通路介导细胞保护。DJ-1 基因的缺失或突变与常染色体隐性早发性 PD 直接相关。DJ-1 在线粒体中具有潜在作用。在这里，我们表明 DJ-1 响应紫外线 B（UVB）照射增加其线粒体分布，并与 Bcl-X（L）结合。DJ-1 和 Bcl-X（L）之间的相互作用是氧化依赖性的。DJ-1（C106A）是 DJ-1 的一种不能被氧化的突变形式，与 Bcl-X（L）的结合能力远低于 DJ-1。此外，DJ-1 通过抑制其泛素化和降解来稳定 Bcl-X（L）蛋白水平，从而通过泛素蛋白酶体系统（UPS）响应 UVB 照射。此外，在 UVB 照射下，敲低 DJ-1 会导致 Bcl-X（L）泛素化和降解增加，从而增加线粒体 Bax、caspase-3 激活和 PARP 切割。这些数据表明，DJ-1 通过其氧化和与线粒体 Bcl-X（L）的关联，保护细胞免受 UVB 诱导的细胞死亡。
