Transcriptional Regulation of DJ-1
DJ-1 is an oncogene and also a causative gene for familial Parkinson’s disease. DJ-1 has various functions, and the oxidative status of a cysteine residue at position 106 (C106) is crucial for determination of the activation level of DJ-1.
DJ-1 binds to many proteins, including various transcription factors, and acts as a coactivator or corepressor for regulating their target genes without direct binding to DNA, thereby affecting various cell functions. DJ-1-regulating transcription factors and their modified proteins are the androgen receptor and its regulatory proteins, p53; polypyrimidine tract-binding protein-associated splicing factor (PSF); Keap1, an inhibitor for nuclear factor erythroid2-related factor 2 (Nrf2); sterol regulatory element-binding protein (SREBP); Ras-responsive element-binding protein (RREB1); signal transducer and activator of transcription 1 (STAT1); and Nurr1. Considering oxidative stress response and dopamine synthesis, the regulation of Nrf2, p53, and PSF by DJ-1 is especially important. In addition, SREBP1 and RREB1 functions that are positively regulated by DJ-1 may participate in the onset and pathogenesis of metabolic syndrome.
DJ-1 is expressed ubiquitously with high levels in the testis and brain and moderate levels in other tissues. Furthermore, DJ-1 is translocated from the cytoplasm to nucleus during the cell cycle after mitogen stimulation, suggesting that DJ-1 has a growth-related function. In this review, we describe how DJ-1 regulates cell growth/death and dopamine synthesis by targeting various transcription factors.
KeywordsDJ-1 Transcription Oxidative stress Parkinson’s disease Cancer
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