Epidermal Growth Factor-dependent Activation of the Extracellular Signal-regulated Kinase Pathway by DJ-1 Protein through Its Direct Binding to c-Raf Protein

Takahashi-Niki, Kazuko; Kato-Ose, Izumi; Murata, Hiroaki; Maita, Hiroshi; Iguchi‐Ariga, Sanae M.M.; Ariga, Hiroyoshi

doi:10.1074/jbc.m115.666271

Cited by 32 publications

(34 citation statements)

References 49 publications

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“…While one group has shown DJ-1 can directly interact with ERK1/2 (Wang et al 2011), other groups have shown that DJ-1 modulates upstream factors in the MAPK cascade, either through direct interaction or by affecting protein expression (Gu et al 2009; Kato et al 2013; Takahashi-Niki et al 2015). …”

Section: 2 Dj-1 Activates the Erk1/2 Pathwaymentioning

confidence: 99%

“…Pulldown assays using GST-DJ-1 mixed with 35 S-labeled c-Raf, and co-immunoprecipitation assays in HeLa (human cervical epithelial adenocarcinoma) and HEK293T cells transfected with FLAG-c-Raf and DJ-1-HA, have shown that DJ-1 binds directly to the kinase domain of c-Raf, the MAPKKK in the ERK signaling pathway (Takahashi-Niki et al 2015). This interaction is enhanced when cells are treated with EGF (Takahashi-Niki et al 2015), which augments c-Raf activation.…”

Section: 2 Dj-1 Activates the Erk1/2 Pathwaymentioning

confidence: 99%

“…However, loss of DJ-1 does not impact the levels of phospho-Ser-259 c-Raf. The reintroduction of DJ-1 into cells derived from DJ-1 KO mice rescues the level of phospho-Ser- 338 c-Raf to control levels (Takahashi-Niki et al 2015). Additionally, when a constitutively active c-Raf fragment (consisting of the kinase domain that binds DJ-1) is incubated with purified DJ-1 and ATP, the fragment exhibits increased autophosphorylation activity in a DJ-1-dose-dependent manner (Takahashi-Niki et al 2015).…”

Section: 2 Dj-1 Activates the Erk1/2 Pathwaymentioning

confidence: 99%

“…The reintroduction of DJ-1 into cells derived from DJ-1 KO mice rescues the level of phospho-Ser- 338 c-Raf to control levels (Takahashi-Niki et al 2015). Additionally, when a constitutively active c-Raf fragment (consisting of the kinase domain that binds DJ-1) is incubated with purified DJ-1 and ATP, the fragment exhibits increased autophosphorylation activity in a DJ-1-dose-dependent manner (Takahashi-Niki et al 2015). This suggests that by binding to c-Raf, DJ-1 stimulates the kinase activity and autophosphorylation of c-Raf at Ser-338, which aids in the activation of the protein and the ERK pathway.…”

Section: 2 Dj-1 Activates the Erk1/2 Pathwaymentioning

confidence: 99%

“…Interestingly, expression of C106S mutant DJ-1 into DJ-1 null cells reportedly does not rescue the level of phospho-Ser-338 c-Raf to control levels, and the binding activity of C106S mutant DJ-1 to c-Raf in pulldown assays is weaker than that of wild-type DJ-1 (Takahashi-Niki et al 2015). The cysteine 106 (Cys-106) residue is highly sensitive to oxidative stress and is essential for the role of DJ-1 as a cytoprotective redox sensor (Taira et al 2004a, b; Canet-Aviles et al 2004; Martinat et al 2004).…”

Section: 2 Dj-1 Activates the Erk1/2 Pathwaymentioning

confidence: 99%

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Regulation of Signal Transduction by DJ-1

Mouradian

2017

Advances in Experimental Medicine and Biology

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The ability of DJ-1 to modulate signal transduction has significant effects on how the cell regulates normal processes such as growth, senescence, apoptosis, and autophagy to adapt to changing environmental stimuli and stresses. Perturbations of DJ-1 levels or function can disrupt the equilibrium of homeostatic signaling networks and set off cascades that play a role in the pathogenesis of conditions such as cancer and Parkinson’s disease. DJ-1 plays a major role in various pathways. It mediates cell survival and proliferation by activating the extracellular signal-regulated kinase (ERK1/2) pathway and the phosphatidylinositol-3-kinase (PI3K)/Akt pathway. It attenuates cell death signaling by inhibiting apoptosis signal-regulating kinase 1 (ASK1) activation as well as by inhibiting mitogen-activated protein kinase kinase kinase 1 (MEKK1/ MAP3K1) activation of downstream apoptotic cascades. It also modulates autophagy through the ERK, Akt, or the JNK/Beclin1 pathways. In addition, DJ-1 regulates the transcription of genes essential for male reproductive function, such as spermatogenesis, by relaying nuclear receptor androgen receptor (AR) signaling. In this chapter, we summarize the ways that DJ-1 regulates these pathways, focusing on how its role in signal transduction contributes to cellular homeostasis and the pathologic states that result from dysregulation.

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Section: 2 Dj-1 Activates the Erk1/2 Pathwaymentioning

confidence: 99%

Section: 2 Dj-1 Activates the Erk1/2 Pathwaymentioning

confidence: 99%

Section: 2 Dj-1 Activates the Erk1/2 Pathwaymentioning

confidence: 99%

Section: 2 Dj-1 Activates the Erk1/2 Pathwaymentioning

confidence: 99%

Section: 2 Dj-1 Activates the Erk1/2 Pathwaymentioning

confidence: 99%

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Regulation of Signal Transduction by DJ-1

Mouradian

2017

Advances in Experimental Medicine and Biology

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PARK7 deficiency inhibits fatty acid β‐oxidation via PTEN to delay liver regeneration after hepatectomy

Wen

Jiao

et al. 2022

Clinical & Translational Med

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Background & aims Transient regeneration–associated steatosis (TRAS) is a process of temporary hepatic lipid accumulation and is essential for liver regeneration by providing energy generated from fatty acid β‐oxidation, but the regulatory mechanism underlying TRAS remains unknown. Parkinsonism‐associated deglycase (Park7)/Dj1 is an important regulator involved in various liver diseases. In nonalcoholic fatty liver diseased mice, induced by a high‐fat diet, Park7 deficiency improves hepatic steatosis, but its role in liver regeneration remains unknown Methods Park7 knockout (Park7−/−), hepatocyte‐specific Park7 knockout (Park7△hep) and hepatocyte‐specific Park7‐Pten double knockout mice were subjected to 2/3 partial hepatectomy (PHx) Results Increased PARK7 expression was observed in the regenerating liver of mice at 36 and 48 h after PHx. Park7−/− and Park7△hep mice showed delayed liver regeneration and enhanced TRAS after PHx. PPARa, a key regulator of β‐oxidation, and carnitine palmitoyltransferase 1a (CPT1a), a rate‐limiting enzyme of β‐oxidation, had substantially decreased expression in the regenerating liver of Park7△hep mice. Increased phosphatase and tensin homolog (PTEN) expression was observed in the liver of Park7△hep mice, which might contribute to delayed liver regeneration in these mice because genomic depletion or pharmacological inhibition of PTEN restored the delayed liver regeneration by reversing the downregulation of PPARa and CPT1a and in turn accelerating the utilization of TRAS in the regenerating liver of Park7△hep mice Conclusion Park7/Dj1 is a novel regulator of PTEN‐dependent fatty acid β‐oxidation, and increasing Park7 expression might be a promising strategy to promote liver regeneration.

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DJ‐1 regulates tyrosine hydroxylase expression through CaMKKβ/CaMKIV/CREB1 pathway in vitro and in vivo

Wang

Hao

et al. 2019

Journal Cellular Physiology

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Lack of dopamine production and neurodegeneration of dopaminergic neurons in the substantia nigra are considered as the major characteristics of Parkinson's disease, a prevalent movement disorder worldwide. DJ-1 mutation leading to loss of its protein functions is a genetic factor of PD. In this study, our results illustrated that DJ-1 can directly interact with Ca 2+ /calmodulin-dependent protein kinase kinase β (CaMKKβ) and modifies the cAMP-responsive element binding protein 1 (CREB1) activity, thus regulates tyrosine hydroxylase (TH) expression. In Dj-1 knockout mouse substantia nigra, the levels of TH and the phosphorylation of CREB1 Ser133 are significantly decreased. Moreover, Dj-1 deficiency suppresses the phosphorylation of CaMKIV (Thr196/200) and CREB1 (Ser133), subsequently inhibits TH expression in vitro.Furthermore, Knockdown of Creb1 abolishes the effects of DJ-1 on TH regulation.Our data reveal a novel pathway in which DJ-1 regulates CaMKKβ/CaMKIV/CREB1 activities to facilitate TH expression.

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Epidermal Growth Factor-dependent Activation of the Extracellular Signal-regulated Kinase Pathway by DJ-1 Protein through Its Direct Binding to c-Raf Protein

Cited by 32 publications

References 49 publications

Regulation of Signal Transduction by DJ-1

Regulation of Signal Transduction by DJ-1

PARK7 deficiency inhibits fatty acid β‐oxidation via PTEN to delay liver regeneration after hepatectomy

DJ‐1 regulates tyrosine hydroxylase expression through CaMKKβ/CaMKIV/CREB1 pathway in vitro and in vivo

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