Identification and characterization of a novel protein that regulates RNA-protein interaction

Hod, Yaacov; Pentyala, Srinivas; Whyard, Terry; el-Maghrabi, M R

doi:10.1002/(sici)1097-4644(19990301)72:3<435::aid-jcb12>3.0.co;2-h

Cited by 179 publications

(87 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The DJ-1 gene encodes a highly conserved protein with 189 amino acids and a molecular weight of ∼20 kDa. DJ-1 has been implicated in diverse cellular processes, including cellular transformation and tumorigenesis [9], [10], [11], transcriptional regulation [12], [13], [14], [15], androgen receptor signaling [16], chaperone [17], [18], spermatogenesis [19], and oxidative stress response [20], [21], [22].…”

Section: Introductionmentioning

confidence: 99%

DJ-1-Dependent Regulation of Oxidative Stress in the Retinal Pigment Epithelium (RPE)

et al. 2013

View full text Add to dashboard Cite

BackgroundDJ-1 is found in many tissues, including the brain, where it has been extensively studied due to its association with Parkinson’s disease. DJ-1 functions as a redox-sensitive molecular chaperone and transcription regulator that robustly protects cells from oxidative stress.MethodologyRetinal pigment epithelial (RPE) cultures were treated with H2O2 for various times followed by biochemical and immunohistological analysis. Cells were transfected with adenoviruses carrying the full-length human DJ-1 cDNA and a mutant construct, which has the cysteine residues at amino acid 46, 53 and 106 mutated to serine (C to S) prior to stress experiments. DJ-1 localization, levels of expression and reactive oxygen species (ROS) generation were also analyzed in cells expressing exogenous DJ-1 under baseline and oxidative stress conditions. The presence of DJ-1 and oxidized DJ-1 was evaluated in human RPE total lysates. The distribution of DJ-1 was assessed in AMD and non-AMD cryosectionss and in isolated human Bruch’s membrane (BM)/choroid from AMD eyes.Principal FindingsDJ-1 in RPE cells under baseline conditions, displays a diffuse cytoplasmic and nuclear staining. After oxidative challenge, more DJ-1 was associated with mitochondria. Increasing concentrations of H2O2 resulted in a dose-dependent increase in DJ-1. Overexpression of DJ-1 but not the C to S mutant prior to exposure to oxidative stress led to significant decrease in the generation of ROS. DJ-1 and oxDJ-1 intensity of immunoreactivity was significantly higher in the RPE lysates from AMD eyes. More DJ-1 was localized to RPE cells from AMD donors with geographic atrophy and DJ-1 was also present in isolated human BM/choroid from AMD eyes.Conclusions/SignificanceDJ-1 regulates RPE responses to oxidative stress. Most importantly, increased DJ-1 expression prior to oxidative stress leads to decreased generation of ROS, which will be relevant for future studies of AMD since oxidative stress is a known factor affecting this disease.

show abstract

Section: Introductionmentioning

confidence: 99%

DJ-1-Dependent Regulation of Oxidative Stress in the Retinal Pigment Epithelium (RPE)

et al. 2013

View full text Add to dashboard Cite

show abstract

“…DJ-1 is reported to interact with RNA and/or localize to the nucleus [67], [68]. Accordingly, it is possible that DJ-1 acts through regulation of transcription/translation/stabilization of PON2 and that direct interaction demonstrated above, is not necessary for the modulation of PON2 by DJ-1.…”

Section: Resultsmentioning

confidence: 97%

DJ-1 Interacts with and Regulates Paraoxonase-2, an Enzyme Critical for Neuronal Survival in Response to Oxidative Stress

Parsanejad

Bourquard²,

et al. 2014

PLoS ONE

View full text Add to dashboard Cite

Loss-of-function mutations in DJ-1 (PARK7) gene account for about 1% of all familial Parkinson's disease (PD). While its physiological function(s) are not completely clear, DJ-1 protects neurons against oxidative stress in both in vitro and in vivo models of PD. The molecular mechanism(s) through which DJ-1 alleviates oxidative stress-mediated damage remains elusive. In this study, we identified Paraoxonase-2 (PON2) as an interacting target of DJ-1. PON2 activity is elevated in response to oxidative stress and DJ-1 is crucial for this response. Importantly, we showed that PON2 deficiency hypersensitizes neurons to oxidative stress induced by MPP+ (1-methyl-4-phenylpyridinium). Conversely, over-expression of PON2 protects neurons in this death paradigm. Interestingly, PON2 effectively rescues DJ-1 deficiency-mediated hypersensitivity to oxidative stress. Taken together, our data suggest a model by which DJ-1 exerts its antioxidant activities, at least partly through regulation of PON2.

show abstract

“…This oxidative stress response may be caused by interactions of DJ-1 with other proteins like protein inhibitor of activated STAT (signal transducer and activator of transcription) (PIASx α ), DJ-1 -binding protein (DJBP), and the RNA-binding protein complex; DJ-1 may also regulate the dismutation of peroxides. 47,48 …”

Section: Autosomal-recessive Forms Of Parkinsonismmentioning

confidence: 99%

Genetics of Parkinson's disease

Gasser¹

2001

Journal of Neurology

186

144

View full text Add to dashboard Cite

Over the past few years, several genes for monogenically inherited forms of Parkinson's disease (PD) have been mapped and/or cloned. In a small number of families with autosomal dominant inheritance and typical Lewy-body pathology, mutations have been identified in the gene for alpha-synuclein. Aggregation of this protein in Lewy-bodies may be a crucial step in the molecular pathogenesis of familial and sporadic PD. On the other hand, mutations in the parkin gene cause autosomal recessive parkinsonism of early onset. In this form of PD, nigral degeneration is not accompanied by Lewy-body formation. Parkin-mutations appear to be a common cause of PD in patients with very early onset. Parkin has been implicated in the cellular protein degradation pathways, as it has been shown that it functions as a ubiquitin ligase. The potential importance of this pathway is also highlighted by the finding of a mutation in the gene for ubiquitin C-terminal hydrolase L1 in another small family with PD. Other loci have been mapped to chromosome 2p and 4p, respectively, in a small number of families with dominantly inherited PD, but those genes have not yet been identified. These findings prove that there are several genetically distinct forms of PD that can be caused by mutations in single genes. On the other hand, there is at present no direct evidence that any of these genes have a direct role in the aetiology of the common sporadic form of PD. Epidemiological, case control, and twin studies, although supporting a genetic contribution to the development of PD, all suggest a clear familial clustering only in a minority of cases. It is therefore widely believed that a combination of interacting genetic and environmental causes may be responsible in this majority of PD-cases. However, studies of gene-environment interactions have not yet produced any convincing results. Nevertheless, the elucidation of the molecular sequence of events leading to nigral degeneration in clearly inherited cases is likely to shed light also on the molecular pathogenesis of the common sporadic form of this disorder.

show abstract

Identification and characterization of a novel protein that regulates RNA-protein interaction

Cited by 179 publications

References 35 publications

DJ-1-Dependent Regulation of Oxidative Stress in the Retinal Pigment Epithelium (RPE)

DJ-1-Dependent Regulation of Oxidative Stress in the Retinal Pigment Epithelium (RPE)

DJ-1 Interacts with and Regulates Paraoxonase-2, an Enzyme Critical for Neuronal Survival in Response to Oxidative Stress

Genetics of Parkinson's disease

Contact Info

Product

Resources

About