KLHL1/MRP2 Mediates Neurite Outgrowth in a Glycogen Synthase Kinase 3β-Dependent Manner

Seng, Seyha; Avraham, Hava; Jiang, Shuxian; Venkatesh, Saritha; Avraham, Shalom

doi:10.1128/mcb.02167-05

Cited by 30 publications

(26 citation statements)

References 50 publications

(55 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Development 136 (14) Drosophila (Nemes et al, 2000) and is described as playing a central role in neurite outgrowth (Seng et al, 2006). In line with this role, Klhl1-null mice exhibit deficits in neurite formation of Purkinje cells (He et al, 2006) and display abnormal gait and progressive loss of motor coordination.…”

Section: Research Articlementioning

confidence: 91%

Identification ofDlk1, PtpruandKlhl1as novel Nurr1 target genes in meso-diencephalic dopamine neurons

et al. 2009

View full text Add to dashboard Cite

The orphan nuclear receptor Nurr1 is essential for the development of meso-diencephalic dopamine (mdDA) neurons and is required, together with the homeobox transcription factor Pitx3, for the expression of genes involved in dopamine metabolism. In order to elucidate the molecular mechanisms that underlie the neuronal deficits in Nurr1 -/-mice, we performed combined gene expression microarrays and ChIP-on-chip analysis and thereby identified Dlk1, Ptpru and Klhl1 as novel Nurr1 target genes in vivo. In line with the previously described cooperativity between Nurr1 and Pitx3, we show that the expression of Ptpru and Klhl1 in mdDA neurons is also dependent on Pitx3. Furthermore, we demonstrate that Nurr1 interacts with the Ptpru promoter directly and requires Pitx3 for full expression of Ptpru in mdDA neurons. By contrast, the expression of Dlk1 is maintained in Pitx3 -/-embryos and is even expanded into the rostral part of the mdDA area, suggesting a unique position of Dlk1 in the Nurr1 and Pitx3 transcriptional cascades. Expression analysis in Dlk1 -/-embryos reveals that Dlk1 is required to prevent premature expression of Dat in mdDA neuronal precursors as part of the multifaceted process of mdDA neuronal differentiation driven by Nurr1 and Pitx3. Taken together, the involvement of Nurr1 and Pitx3 in the expression of novel target genes involved in important neuronal processes such as neuronal patterning, axon outgrowth and terminal differentiation, opens up new avenues to study the properties of mdDA neurons during development and in neuronal pathology as observed in Parkinson's disease.

show abstract

Section: Research Articlementioning

confidence: 91%

Identification ofDlk1, PtpruandKlhl1as novel Nurr1 target genes in meso-diencephalic dopamine neurons

et al. 2009

View full text Add to dashboard Cite

show abstract

“…Despite similar domain organization their cellular localizations were found to be different. While MAYVEN, MRP2, and KEAP1 are localized in the cytoplasm, NRP/B is confined to the nucleus (17,20,24). In the presence of NRF2, NRP/B actively induced the transcriptional activity of HO1, whereas KEAP1 inhibited this activity (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…Specific Activation of NRF2 Target Genes by NRP/B-We previously cloned and characterized several Kelch-related family members including NRP/B (19), MRP2 (24), and MAYVEN (29). These proteins have similar domain organization (Fig.…”

Section: Expression Of Nrp/b In Neuronal Cells-nrp/b Has Beenmentioning

confidence: 99%

“…KEAP1, another Kelch family member, functions as transcriptional repressor for NRF2 (8), whereas NRP/B is an enhancer for NRF2 activity (17,20). MRP2 is involved in glycogen synthase kinase 3␤-mediated neuronal differentiation (24) and process elongation in oligodendrocytes (25,31). MAYVEN is also essential for FYN-modulated process elongation in oligodendrocytes (25).…”

Section: Expression Of Nrp/b In Neuronal Cells-nrp/b Has Beenmentioning

confidence: 99%

“…MAYVEN is also essential for FYN-modulated process elongation in oligodendrocytes (25). Whereas KEAP1, MRP2, and MAYVEN are endogenously localized in the cytoplasm (8,24,25), NRP/B is endogenously localized in the nucleus (19,32). We examined the differential effects of these proteins on NRF2-mediated HO1 transcriptional activity using a luciferase reporter assay.…”

Section: Expression Of Nrp/b In Neuronal Cells-nrp/b Has Beenmentioning

confidence: 99%

See 2 more Smart Citations

Nuclear Matrix Protein (NRP/B) Modulates the Nuclear Factor (Erythroid-derived 2)-related 2 (NRF2)-dependent Oxidative Stress Response

Seng

Avraham

Birrane

et al. 2010

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Reactive molecules have diverse effects on cells and contribute to several pathological conditions. Cells have evolved complex protective systems to neutralize these molecules and restore redox homeostasis. Previously, we showed that association of nuclear factor (NF)-erythroid-derived 2 (E2)-related factor 2 (NRF2) with the nuclear matrix protein NRP/B was essential for the transcriptional activity of NRF2 target genes in tumor cells. The present study demonstrates the molecular mechanism by which NRP/B, via NRF2, modulates the transcriptional activity of antioxidant response element ( Mammalian cells are exposed to reactive molecules originating from several exogenous and endogenous sources (1, 2). These molecules include reactive oxygen species, electrophilic chemicals, and heavy metals, which induce oxidative stress that impairs cellular functions and results in diverse pathological conditions, such as cancer, cardiovascular disease, diabetes, and neurodegenerative disorders (2-5). In response to these reactive molecules, cells have evolved multiple protective mechanisms to neutralize and clear toxic molecules and restore cellular redox homeostasis. One of these mechanisms is modulated by the nuclear factor (NF) 2 -E2-related factor 2 (NRF2) protein (6), which binds to ARE promoter sequences, leading to the coordinated up-regulation of ARE-driven detoxifying and antioxidant genes (7-11). The NRF2 system confers a protective effect on mammalian cells from a variety of toxic insults including carcinogens, reactive oxygen species, diesel exhaust, inflammation, calcium disturbance, UV light, and cigarette smoke (6).Kelch-related proteins contain an N-terminal BTB (Broadcomplex, Tramtrack, Bric-a-brac) domain that is primarily found in zinc finger proteins and functions as a homo-or heterodimerization domain (12, 13) and a C-terminal Kelch repeat or ␤-propeller domain that binds actin tails and has important roles in protein folding and as a protein-protein interaction module (12, 13). Multiprotein complexes formed through contact sites in ␤-propeller domains (14) are believed to be important for gene expression, cytoskeletal maintenance (15, 16), and controlling cellular organization and morphology (15, 16). Importantly, alterations or mutations in Kelch-related proteins have been found in numerous tumors (14, 17) and neurodegenerative disorders (18). The cytoplasmic protein Kelch-like ECH-associated protein 1 (KEAP1) and the nuclear NRP/B are both members of the Kelch-related family (8,19). The localization of these proteins is important for regulation of the NRF2 pathway in which KEAP1 and NRP/B/ENC1 suppress and enhance, respectively, NRF2-mediated phase II detoxifying and antioxidant enzymes in response to oxidative stress (8,17,20).Six functional domains of NRF2, termed NRF2 ECH homology (Neh) 1-6, have been identified and found to be highly conserved in various species (8). Neh1 is a bZip motif that mediates DNA binding and participates in heterodimerization with 2 The abbreviations used are: NF, nuclear f...

show abstract

Silencing Huntington’s Disease Gene with RNAi

Friedlander

2010

RNA Technologies and Their Applications

View full text Add to dashboard Cite

KLHL1/MRP2 Mediates Neurite Outgrowth in a Glycogen Synthase Kinase 3β-Dependent Manner

Cited by 30 publications

References 50 publications

Identification ofDlk1, PtpruandKlhl1as novel Nurr1 target genes in meso-diencephalic dopamine neurons

Identification ofDlk1, PtpruandKlhl1as novel Nurr1 target genes in meso-diencephalic dopamine neurons

Nuclear Matrix Protein (NRP/B) Modulates the Nuclear Factor (Erythroid-derived 2)-related 2 (NRF2)-dependent Oxidative Stress Response

Silencing Huntington’s Disease Gene with RNAi

Contact Info

Product

Resources

About