Genomes and Genes
Gene Symbol: Park7
Description: Parkinson disease (autosomal recessive, early onset) 7
Alias: DJ-1, Dj1, protein/nucleic acid deglycase DJ-1, RNA-binding protein regulatory subunit, maillard deglycase, parkinson disease protein 7 homolog, parkinsonism-associated deglycase, protein DJ-1, protein deglycase DJ-1
- Sajjad M, Green E, Miller Fleming L, Hands S, Herrera F, Campesan S, et al. DJ-1 modulates aggregation and pathogenesis in models of Huntington's disease. Hum Mol Genet. 2014;23:755-66 pubmed publisher..Our findings clearly establish DJ-1 as a potential therapeutic target for HD and provide the basis for further studies into the role of DJ-1 in protein misfolding diseases. ..
- Manning Bog A, Caudle W, Perez X, Reaney S, Paletzki R, Isla M, et al. Increased vulnerability of nigrostriatal terminals in DJ-1-deficient mice is mediated by the dopamine transporter. Neurobiol Dis. 2007;27:141-50 pubmed..control striatum. Thus, under null DJ-1 conditions, DAT changes likely contribute to altered DA neurotransmission and enhanced sensitivity to toxins that utilize DAT for nigrostriatal entry. ..
- Kato I, Maita H, Takahashi Niki K, Saito Y, Noguchi N, Iguchi Ariga S, et al. Oxidized DJ-1 inhibits p53 by sequestering p53 from promoters in a DNA-binding affinity-dependent manner. Mol Cell Biol. 2013;33:340-59 pubmed publisher..These results indicate that DJ-1 inhibits the expression of p53 target genes and depend on p53 DNA-binding affinity and oxidation of DJ-1 C106. ..
- Krebiehl G, Ruckerbauer S, Burbulla L, Kieper N, Maurer B, Waak J, et al. Reduced basal autophagy and impaired mitochondrial dynamics due to loss of Parkinson's disease-associated protein DJ-1. PLoS ONE. 2010;5:e9367 pubmed publisher..Our study provides evidence for a critical role of DJ-1 in mitochondrial homeostasis by connecting basal autophagy and mitochondrial integrity in Parkinson's disease. ..
- Bonifati V, Rizzu P, van Baren M, Schaap O, Breedveld G, Krieger E, et al. Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism. Science. 2003;299:256-9 pubmedThe DJ-1 gene encodes a ubiquitous, highly conserved protein. Here, we show that DJ-1 mutations are associated with PARK7, a monogenic form of human parkinsonism...
- Kim J, Choi D, Jeong H, Kim J, Kim D, Choi S, et al. DJ-1 facilitates the interaction between STAT1 and its phosphatase, SHP-1, in brain microglia and astrocytes: A novel anti-inflammatory function of DJ-1. Neurobiol Dis. 2013;60:1-10 pubmed publisher..In this study, we demonstrate a novel mechanism by which DJ-1 (PARK7), an early onset autosomal-recessive PD gene, negatively regulates inflammatory responses of astrocytes and ..
- Pham T, Giesert F, Röthig A, Floss T, Kallnik M, Weindl K, et al. DJ-1-deficient mice show less TH-positive neurons in the ventral tegmental area and exhibit non-motoric behavioural impairments. Genes Brain Behav. 2010;9:305-17 pubmed publisherLoss of function of DJ-1 (PARK7) is associated with autosomal recessive early-onset Parkinson's disease (PD), one of the major age-related neurological diseases...
- Kim Y, Kitaura H, Taira T, Iguchi Ariga S, Ariga H. Oxidation of DJ-1-dependent cell transformation through direct binding of DJ-1 to PTEN. Int J Oncol. 2009;35:1331-41 pubmed..These results suggest that the oxidative status of DJ-1 regulates PTEN activity, leading to cell proliferation and transformation. ..
- Mullett S, Di Maio R, Greenamyre J, Hinkle D. DJ-1 expression modulates astrocyte-mediated protection against neuronal oxidative stress. J Mol Neurosci. 2013;49:507-11 pubmed publisherDJ-1 deficiency is a cause of genetic Parkinson's disease (PARK7 PD). In sporadic Parkinson's disease (PD), however, DJ-1 is abundantly expressed in reactive astrocytes. This may represent a compensatory protective response...
- Yamashita S, Mori A, Kimura E, Mita S, Maeda Y, Hirano T, et al. DJ-1 forms complexes with mutant SOD1 and ameliorates its toxicity. J Neurochem. 2010;113:860-70 pubmed publisher..DJ-1 - a causative agent of familial Parkinson's disease PARK7 - is responsible for inducing antioxidative reaction...
- Heo J, Park J, Kim S, Seo K, Han J, Lee S, et al. DJ-1 null dopaminergic neuronal cells exhibit defects in mitochondrial function and structure: involvement of mitochondrial complex I assembly. PLoS ONE. 2012;7:e32629 pubmed publisher..These mitochondrial defects induced by DJ-1mutation may be a pathological mechanism for the degeneration of dopaminergic neurons in Parkinson's disease. ..
- Guzman J, Sanchez Padilla J, Wokosin D, Kondapalli J, Ilijic E, Schumacker P, et al. Oxidant stress evoked by pacemaking in dopaminergic neurons is attenuated by DJ-1. Nature. 2010;468:696-700 pubmed publisher..Knocking out DJ-1 (also known as PARK7 in humans and Park7 in mice), which is a gene associated with an early-onset form of Parkinson's disease, ..
- Andres Mateos E, Perier C, Zhang L, Blanchard Fillion B, Greco T, Thomas B, et al. DJ-1 gene deletion reveals that DJ-1 is an atypical peroxiredoxin-like peroxidase. Proc Natl Acad Sci U S A. 2007;104:14807-12 pubmed..Taken together these data indicate that the DJ-1 KO mice have a deficit in scavenging mitochondrial H(2)O(2) due to the physiological function of DJ-1 as an atypical peroxiredoxin-like peroxidase. ..
- Raman A, Chou V, Atienza Duyanen J, Di Monte D, Bellinger F, Manning Bog A. Evidence of oxidative stress in young and aged DJ-1-deficient mice. FEBS Lett. 2013;587:1562-70 pubmed publisher..These changes were concomitant with increased striatal dopamine levels and uptake. Thus, increased oxidants and diminished protein quality control may contribute to nigral oxidative damage with aging in the model. ..
- Vasseur S, Afzal S, Tardivel Lacombe J, Park D, Iovanna J, Mak T. DJ-1/PARK7 is an important mediator of hypoxia-induced cellular responses. Proc Natl Acad Sci U S A. 2009;106:1111-6 pubmed publisherIn cancer, DJ-1/PARK7 acts as an oncogene that drives Akt-mediated cell survival...
- Im J, Lee K, Woo J, Junn E, Mouradian M. DJ-1 induces thioredoxin 1 expression through the Nrf2 pathway. Hum Mol Genet. 2012;21:3013-24 pubmed publisher..These findings provide a new mechanism to support the antioxidant function of DJ-1 by increasing Trx1 expression via Nrf2-mediated transcriptional induction. ..
- Billia F, Hauck L, Grothe D, Konecny F, Rao V, Kim R, et al. Parkinson-susceptibility gene DJ-1/PARK7 protects the murine heart from oxidative damage in vivo. Proc Natl Acad Sci U S A. 2013;110:6085-90 pubmed publisher..Our results provide compelling in vivo evidence that DJ-1 is a unique and nonredundant antioxidant that functions independent of other antioxidative pathways in the cellular defense against ROS. ..
- Chen L, Cagniard B, Mathews T, Jones S, Koh H, Ding Y, et al. Age-dependent motor deficits and dopaminergic dysfunction in DJ-1 null mice. J Biol Chem. 2005;280:21418-26 pubmed..These data represent the in vivo evidence that loss of DJ-1 function alters nigrostriatal dopaminergic function and produces motor deficits. ..
- Görner K, Holtorf E, Waak J, Pham T, Vogt Weisenhorn D, Wurst W, et al. Structural determinants of the C-terminal helix-kink-helix motif essential for protein stability and survival promoting activity of DJ-1. J Biol Chem. 2007;282:13680-91 pubmedMutations in the PARK7 gene encoding DJ-1 cause autosomal recessive Parkinson disease...
- Hao L, Giasson B, Bonini N. DJ-1 is critical for mitochondrial function and rescues PINK1 loss of function. Proc Natl Acad Sci U S A. 2010;107:9747-52 pubmed publisherMutations or deletions in PARKIN/PARK2, PINK1/PARK6, and DJ-1/PARK7 lead to autosomal recessive parkinsonism. In Drosophila, deletions in parkin and pink1 result in swollen and dysfunctional mitochondria in energy-demanding tissues...
- Usami Y, Hatano T, Imai S, Kubo S, Sato S, Saiki S, et al. DJ-1 associates with synaptic membranes. Neurobiol Dis. 2011;43:651-62 pubmed publisher..DJ-1 is a causative gene for autosomal recessive form of PARK7-linked early-onset PD...
- Irrcher I, Aleyasin H, Seifert E, Hewitt S, Chhabra S, Phillips M, et al. Loss of the Parkinson's disease-linked gene DJ-1 perturbs mitochondrial dynamics. Hum Mol Genet. 2010;19:3734-46 pubmed publisher..DJ-1 (PARK7) is a recently identified recessive familial PD gene...
- Kim Y, Kitaura H, Iguchi Ariga S, Ariga H. DJ-1, an oncogene and causative gene for familial Parkinson's disease, is essential for SV40 transformation in mouse fibroblasts through up-regulation of c-Myc. FEBS Lett. 2010;584:3891-5 pubmed publisher..We also found that DJ-1 directly bound to LT and that the expression level of c-Myc in transformed cells was parallel to that of DJ-1. These findings indicate that DJ-1 is essential for SV40 transformation. ..
- Yang W, Chen L, Ding Y, Zhuang X, Kang U. Paraquat induces dopaminergic dysfunction and proteasome impairment in DJ-1-deficient mice. Hum Mol Genet. 2007;16:2900-10 pubmed..In conclusion, this study raises the possibility that environmental and genetic factors might cooperatively involve the mechanisms underlying proteasome impairment in PD brains. ..
- McNally R, Davis B, Clements C, Accavitti Loper M, Mak T, Ting J. DJ-1 enhances cell survival through the binding of Cezanne, a negative regulator of NF-kappaB. J Biol Chem. 2011;286:4098-106 pubmed publisherHeightened DJ-1 (Park7) expression is associated with a reduction in chemotherapeutic-induced cell death and poor prognosis in several cancers, whereas the loss of DJ-1 function is found in a subgroup of Parkinson disease associated with ..
- Yamaguchi S, Yamane T, Takahashi Niki K, Kato I, Niki T, Goldberg M, et al. Transcriptional activation of low-density lipoprotein receptor gene by DJ-1 and effect of DJ-1 on cholesterol homeostasis. PLoS ONE. 2012;7:e38144 pubmed publisherDJ-1 is a novel oncogene and also causative gene for familial Parkinson's disease park7. DJ-1 has multiple functions that include transcriptional regulation, anti-oxidative reaction and chaperone and mitochondrial regulation...
- Akazawa Y, Saito Y, Hamakubo T, Masuo Y, Yoshida Y, Nishio K, et al. Elevation of oxidized DJ-1 in the brain and erythrocytes of Parkinson disease model animals. Neurosci Lett. 2010;483:201-5 pubmed publisher..These results suggest that the oxidative modification of DJ-1 in the brain and erythrocytes is involved in the pathogenesis of PD in animal models...
- Zhang L, Shimoji M, Thomas B, Moore D, Yu S, Marupudi N, et al. Mitochondrial localization of the Parkinson's disease related protein DJ-1: implications for pathogenesis. Hum Mol Genet. 2005;14:2063-73 pubmed..Our findings of DJ-1's mitochondrial localization may have important implications for understanding the pathogenesis of PD. ..
- Chandran J, Lin X, Zapata A, Hoke A, Shimoji M, Moore S, et al. Progressive behavioral deficits in DJ-1-deficient mice are associated with normal nigrostriatal function. Neurobiol Dis. 2008;29:505-14 pubmed publisher..Taken together, our findings suggest that loss of DJ-1 leads to progressive behavioral changes without significant alterations in nigrostriatal dopaminergic and spinal motor systems. ..
- Aleyasin H, Rousseaux M, Marcogliese P, Hewitt S, Irrcher I, Joselin A, et al. DJ-1 protects the nigrostriatal axis from the neurotoxin MPTP by modulation of the AKT pathway. Proc Natl Acad Sci U S A. 2010;107:3186-91 pubmed publisherLoss-of-function DJ-1 (PARK7) mutations have been linked with a familial form of early onset Parkinson disease. Numerous studies have supported the role of DJ-1 in neuronal survival and function...
- Hayashi T, Ishimori C, Takahashi Niki K, Taira T, Kim Y, Maita H, et al. DJ-1 binds to mitochondrial complex I and maintains its activity. Biochem Biophys Res Commun. 2009;390:667-72 pubmed publisher..DJ-1, a causative gene product of a familial form of Parkinson's disease, PARK7, plays roles in transcriptional regulation and anti-oxidative stress...
- Jain D, Jain R, Eberhard D, Eglinger J, Bugliani M, Piemonti L, et al. Age- and diet-dependent requirement of DJ-1 for glucose homeostasis in mice with implications for human type 2 diabetes. J Mol Cell Biol. 2012;4:221-30 pubmed publisher..Our data suggest that DJ-1 is more generally involved in age- and lifestyle-related human diseases and show for the first time that DJ-1 plays a key role in glucose homeostasis and might serve as a novel drug target for T2DM. ..
- Mitsumoto A, Nakagawa Y. DJ-1 is an indicator for endogenous reactive oxygen species elicited by endotoxin. Free Radic Res. 2001;35:885-93 pubmed..8 might increase in response to endogenously produced ROS, probably due to activation of NADPH oxidase, and imply that DJ-1 may be useful as an endogenous indicator of oxidative stress status in vivo. ..
- Martinat C, Shendelman S, Jonason A, Leete T, Beal M, Yang L, et al. Sensitivity to oxidative stress in DJ-1-deficient dopamine neurons: an ES- derived cell model of primary Parkinsonism. PLoS Biol. 2004;2:e327 pubmed..These data are consistent with a protective role for DJ-1, and demonstrate the utility of genetically modified embryonic stem cell-derived neurons as cellular models of neuronal disorders. ..
- Goldberg M, Pisani A, Haburcak M, Vortherms T, Kitada T, Costa C, et al. Nigrostriatal dopaminergic deficits and hypokinesia caused by inactivation of the familial Parkinsonism-linked gene DJ-1. Neuron. 2005;45:489-96 pubmed..Furthermore, DJ-1(-/-) mice displayed hypoactivity in the open field. Collectively, our findings suggest an essential role for DJ-1 in dopaminergic physiology and D2 receptor-mediated functions...
- Lev N, Ickowicz D, Barhum Y, Lev S, Melamed E, Offen D. DJ-1 protects against dopamine toxicity. J Neural Transm (Vienna). 2009;116:151-60 pubmed publisher..This mechanism elucidates how mutations in DJ-1 prompt PD and imply that modulation of DJ-1 may serve as a novel neuroprotective modality. ..
- van der Brug M, Blackinton J, Chandran J, Hao L, Lal A, Mazan Mamczarz K, et al. RNA binding activity of the recessive parkinsonism protein DJ-1 supports involvement in multiple cellular pathways. Proc Natl Acad Sci U S A. 2008;105:10244-9 pubmed publisher..These data implicate a single mechanism for the pleiotropic effects of DJ-1 in different model systems, namely that the protein binds multiple RNA targets in an oxidation-dependent manner. ..
- Thomas K, McCoy M, Blackinton J, Beilina A, Van Der Brug M, Sandebring A, et al. DJ-1 acts in parallel to the PINK1/parkin pathway to control mitochondrial function and autophagy. Hum Mol Genet. 2011;20:40-50 pubmed publisher..None of the three proteins complex together using size exclusion chromatography. These data suggest that DJ-1 works in parallel to the PINK1/parkin pathway to maintain mitochondrial function in the presence of an oxidative environment. ..
- Chen J, Li L, Chin L. Parkinson disease protein DJ-1 converts from a zymogen to a protease by carboxyl-terminal cleavage. Hum Mol Genet. 2010;19:2395-408 pubmed publisher..Our findings support a role for DJ-1 protease in cellular defense against oxidative stress and have important implications for understanding and treating PD. ..
- Yokota T, Sugawara K, Ito K, Takahashi R, Ariga H, Mizusawa H. Down regulation of DJ-1 enhances cell death by oxidative stress, ER stress, and proteasome inhibition. Biochem Biophys Res Commun. 2003;312:1342-8 pubmed..These results suggest that loss of protective activity of DJ-1 from neuro-toxicity induced by these stresses contributes to neuronal cell death in AR-EOP with mutant DJ-1. ..
- Sheng C, Heng X, Zhang G, Xiong R, Li H, Zhang S, et al. DJ-1 deficiency perturbs microtubule dynamics and impairs striatal neurite outgrowth. Neurobiol Aging. 2013;34:489-98 pubmed publisher..Our results revealed a novel role of DJ-1 in the regulation of microtubule dynamics and suggested that striatal impairments may also play an important role as loss of DA neurons in the pathogenesis of PD. ..
- Nishinaga H, Takahashi Niki K, Taira T, Andreadis A, Iguchi Ariga S, Ariga H. Expression profiles of genes in DJ-1-knockdown and L 166 P DJ-1 mutant cells. Neurosci Lett. 2005;390:54-9 pubmed..These findings suggest that DJ-1 regulates expressions of genes for which functions are thought to be related to cell death or neurodegeneration. ..
- Im J, Lee K, Junn E, Mouradian M. DJ-1 protects against oxidative damage by regulating the thioredoxin/ASK1 complex. Neurosci Res. 2010;67:203-8 pubmed publisher..These findings point to yet another mechanism through which DJ-1 has anti-oxidant and cytoprotective properties by regulating the Trx1/ASK1 complex and controlling the availability of ASK1 to effect apoptosis. ..
- Inberg A, Linial M. Protection of pancreatic beta-cells from various stress conditions is mediated by DJ-1. J Biol Chem. 2010;285:25686-98 pubmed publisher..DJ-1 (park7) is a multifunctional protein implicated in familial Parkinsonism and neuroprotection in response to oxidative ..
- Rousseaux M, Marcogliese P, Qu D, Hewitt S, Seang S, Kim R, et al. Progressive dopaminergic cell loss with unilateral-to-bilateral progression in a genetic model of Parkinson disease. Proc Natl Acad Sci U S A. 2012;109:15918-23 pubmedDJ-1 mutations cause autosomal recessive early-onset Parkinson disease (PD). We report a model of PD pathology: the DJ1-C57 mouse...
- Lee J, Song J, Kwon K, Jang S, Kim C, Baek K, et al. Human DJ-1 and its homologs are novel glyoxalases. Hum Mol Genet. 2012;21:3215-25 pubmed publisher..elegans lacking cDJR-1.2, another DJ-1 homolog expressed primarily in the head region, including neurons. Our findings that DJ-1 serves as scavengers for reactive carbonyl species may provide a new insight into the causation of PD. ..
- Morris C, O Brien K, Gibson A, Hardy J, Singleton A. Polymorphism in the human DJ-1 gene is not associated with sporadic dementia with Lewy bodies or Parkinson's disease. Neurosci Lett. 2003;352:151-3 pubmed..The DJ-1 gene does not appear to be a significant risk factor for late onset Lewy body disease in this population. ..
- Yamane T, Suzui S, Kitaura H, Takahashi Niki K, Iguchi Ariga S, Ariga H. Transcriptional activation of the cholecystokinin gene by DJ-1 through interaction of DJ-1 with RREB1 and the effect of DJ-1 on the cholecystokinin level in mice. PLoS ONE. 2013;8:e78374 pubmed publisher..Furthermore, the reduced CCK level in the serum from DJ-1-knockout mice compared to that from wild-type mice was observed. This is the first report showing that DJ-1 participates in peptide hormone synthesis. ..
- Chien C, Lee M, Liou H, Liou H, Fu W. Growth hormone is increased in the lungs and enhances experimental lung metastasis of melanoma in DJ-1 KO mice. BMC Cancer. 2016;16:871 pubmed..These results indicate that up-regulation of GH in the lungs of DJ-1 KO mice may enhance the malignancy of B16F10 cells and nodule formation in pulmonary metastasis of melanoma. ..
- Zhou W, Barkow J, Freed C. Running wheel exercise reduces α-synuclein aggregation and improves motor and cognitive function in a transgenic mouse model of Parkinson's disease. PLoS ONE. 2017;12:e0190160 pubmed publisher..Our results suggest that exercise may slow the progression of Parkinson's disease by preventing abnormal protein aggregation in brain. ..
- Shi S, Lu S, Sivasubramaniyam T, Revelo X, Cai E, Luk C, et al. DJ-1 links muscle ROS production with metabolic reprogramming and systemic energy homeostasis in mice. Nat Commun. 2015;6:7415 pubmed publisher..Our data suggest that promoting mitochondrial uncoupling may be a potential strategy for the treatment of obesity-associated metabolic disorders. ..
- Björkblom B, Adilbayeva A, Maple Grødem J, Piston D, Okvist M, Xu X, et al. Parkinson disease protein DJ-1 binds metals and protects against metal-induced cytotoxicity. J Biol Chem. 2013;288:22809-20 pubmed publisher..The study indicates that even a small genetic alteration can sensitize cells to metal-induced cell death, a finding that may revive the interest in exogenous factors in the etiology of PD. ..
- Vasseur S, Afzal S, Tomasini R, Guillaumond F, Tardivel Lacombe J, Mak T, et al. Consequences of DJ-1 upregulation following p53 loss and cell transformation. Oncogene. 2012;31:664-70 pubmed publisher..Importantly, our study highlights that during transformation, DJ-1 is having a key role in the p53-regulated AKT pathway and p53-driven oxidative-stress response. ..
- Parsanejad M, Zhang Y, Qu D, Irrcher I, Rousseaux M, Aleyasin H, et al. Regulation of the VHL/HIF-1 pathway by DJ-1. J Neurosci. 2014;34:8043-50 pubmed publisherDJ-1 (PARK7) is a gene linked to autosomal recessive Parkinson disease (PD). We showed previously that DJ-1 loss sensitizes neurons in models of PD and stroke...
- Seyfarth K, Poschmann G, Rozman J, Fromme T, Rink N, Hofmann A, et al. The development of diet-induced obesity and associated metabolic impairments in Dj-1 deficient mice. J Nutr Biochem. 2015;26:75-81 pubmed publisher..We demonstrate that the development of diet-induced obesity (DIO) Dj-1(-/-) mice is according to wild-type mice with the exception of transient higher gains in fat mass at the expense of lean mass after 14 weeks of feeding. ..