title: Oxidized DJ-1 interacts with the mitochondrial protein BCL-XL.
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).
authors.affiliation: 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.
authors.forename: Haigang
authors.initials: H
authors.lastname: Ren
authors.forename: Kai
authors.initials: K
authors.lastname: Fu
authors.forename: Dan
authors.initials: D
authors.lastname: Wang
authors.forename: Chenchen
authors.initials: C
authors.lastname: Mu
authors.forename: Guanghui
authors.initials: G
authors.lastname: Wang
mesh_terms: D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D005786:Gene Expression Regulation; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism; D015513:Oncogene Proteins / Q000378:metabolism*; D010300:Parkinson Disease / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011485:Protein Binding; D000071617:Protein Deglycase DJ-1; D013347:Subcellular Fractions / Q000378:metabolism; D025801:Ubiquitin / Q000737:chemistry; D014466:Ultraviolet Rays; D051020:bcl-X Protein / Q000378:metabolism*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D015513:Oncogene Proteins; D025801:Ubiquitin; D051020:bcl-X Protein; D011065:Poly(ADP-ribose) Polymerases; D005982:Glutathione Transferase; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1; D053148:Caspase 3