Introduction to a Thematic Issue for WWOX

Chang, Nan Shan

doi:10.1177/1535370215574226

Cited by 15 publications

(24 citation statements)

References 27 publications

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“…ZDHH8 has been reported to be associated with susceptibility to schizophrenia (Mukai et al 2004), ZNF74 has been also reported o be associated with age-at-onset of schizophrenia (Takase et al 2001), and KLHL22 plays a role in ubiquitination (Metzger et al 2013). The WW domaincontaining oxidoreductase (WWOX), a likely tumor suppressor gene, is linked to neuronal development (Chang 2015). Early connection between WWOX and neurological disorders came from animal models that demonstrated epilepsy and ataxia caused by WWOX loss (Suzuki 2009 andMallaret 2014).…”

Section: Discussionmentioning

confidence: 99%

Novel mutations in WWOX, RARS2, and C10orf2 genes in consanguineous Arab families with intellectual disability

et al. 2016

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Intellectual disability is a heterogeneous disease with many genes and mutations influencing the phenotype. Consanguineous families constitute a rich resource for the identification of rare variants causing autosomal recessive disease, due to the effects of inbreeding. Here, we examine three consanguineous Arab families, recruited in a quest to identify novel genes/mutations. All the families had multiple offspring with non-specific intellectual disability. We identified homozygosity (autozygosity) intervals in those families through SNP genotyping and whole exome sequencing, with variants filtered using Ingenuity Variant Analysis (IVA) software. The families showed heterogeneity and novel mutations in three different genes known to be associated with intellectual disability. These mutations were not found in 514 ethnically matched control chromosomes. p.G410C in WWOX, p.H530Y in RARS2, and p.I69F in C10orf2 are novel changes that affect protein function and could give new insights into the development and function of the central nervous system.

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Section: Discussionmentioning

confidence: 99%

Novel mutations in WWOX, RARS2, and C10orf2 genes in consanguineous Arab families with intellectual disability

et al. 2016

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“…Here, we investigated whether tumor suppressor WW domain-containing oxidoreductase, known as WWOX, FOR, or WOX1, participates in the early signaling of T cell acute lymphoblastic leukemia (T-ALL) maturation. WWOX plays a crucial role in tumor suppression, metabolism, ataxia, epilepsy, neural disorders, neuronal damages and degeneration, and anti-viral immune responses (13)(14)(15)(16)(17)(18)(19)(20)(21)(22). Here, we showed that WWOX binds IB␣ and ERK and the complex localizes, in part, in the mitochondria of immature T lymphoid cells.…”

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confidence: 81%

Role of WW Domain-containing Oxidoreductase WWOX in Driving T Cell Acute Lymphoblastic Leukemia Maturation

Huang

Wan

Lin

et al. 2016

Journal of Biological Chemistry

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131

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Whether tumor suppressor WWOX (WW domain-containing oxidoreductase) stimulates immune cell maturation is largely unknown. Here, we determined that Tyr-33-phosphorylated WWOX physically binds non-phosphorylated ERK and IκBα in immature acute lymphoblastic leukemia MOLT-4 T cells and in the naïve mouse spleen. The IκBα·ERK·WWOX complex was shown to localize, in part, in the mitochondria. WWOX prevents IκBα from proteasomal degradation. Upon stimulating MOLT-4 with ionophore A23187/phorbol myristate acetate, endogenous IκBα and ERK undergo rapid phosphorylation in <5 min, and subsequently WWOX is Tyr-33 and Tyr-287 de-phosphorylated and Ser-14 phosphorylated. Three hours later, IκBα starts to degrade, and ERK returns to basal or non-phosphorylation, and this lasts for the next 12 h. Finally, expression of CD3 and CD8 occurs in MOLT-4 along with reappearance of the IκBα·ERK·WWOX complex near 24 h. Inhibition of ERK phosphorylation by U0126 or IκBα degradation by MG132 prevents MOLT-4 maturation. By time-lapse FRET microscopy, IκBα·ERK·WWOX complex exhibits an increased binding strength by 1–2-fold after exposure to ionophore A23187/phorbol myristate acetate for 15–24 h. Meanwhile, a portion of ERK and WWOX relocates to the nucleus, suggesting their role in the induction of CD3 and CD8 expression in MOLT-4.

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“…The specificity of the antisera was tested using the synthetic peptides to block immunoblots. Where indicated, Western blotting was carried out as described [1] , [8] , [10] , [14] . In addition, we generated antibody against self-polymerizing SH3GLB2 (SH3 domain-containing GRB2-like endophilin B2), using the synthetic peptide NH-CDACKARLKKAKAAEAK-COOH (amino acid 170–185).…”

Section: Methodsmentioning

confidence: 99%

“…Zinc finger-like protein that regulates apoptosis (Zfra) is a 31-amino-acid protein, possessing two cysteines and one histidine in the amino acid sequence [1] , [2] , [3] , [4] . Zfra is one of the binding proteins for tumor suppressor WW domain-containing oxidoreductase (WWOX, FOR, or WOX1) [5] , [6] , [7] , [8] , [9] . Substantial evidence shows that WWOX is involved in neural diseases.…”

Section: Introductionmentioning

confidence: 99%

Zfra restores memory deficits in Alzheimer's disease triple‐transgenic mice by blocking aggregation of TRAPPC6AΔ, SH3GLB2, tau, and amyloid β, and inflammatory NF‐κB activation

Lee

Shih

Lin

et al. 2017

A&D Transl Res & Clin Interv

182

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IntroductionZinc finger-like protein that regulates apoptosis (Zfra) is a naturally occurring 31-amino-acid protein. Synthetic peptides Zfra1–31 and Zfra4–10 are known to effectively block the growth of many types of cancer cells.MethodsTen-month-old triple-transgenic (3×Tg) mice for Alzheimer's disease (AD) received synthetic Zfra peptides via tail vein injections, followed by examining restoration of memory deficits.ResultsZfra significantly downregulated TRAPPC6AΔ, SH3GLB2, tau, and amyloid β (Αβ) aggregates in the brains of 3×Tg mice and effectively restored their memory capabilities. Zfra inhibited melanoma-induced neuronal death in the hippocampus and plaque formation in the cortex. Mechanistically, Zfra blocked the aggregation of amyloid β 42 and many serine-containing peptides in vitro, suppressed tumor necrosis factor–mediated NF-κB activation, and bound cytosolic proteins for accelerating their degradation in ubiquitin/proteasome-independent manner.DiscussionZfra peptides exhibit a strong efficacy in blocking tau aggregation and amyloid Αβ formation and restore memory deficits in 3×Tg mice, suggesting its potential for treatment of AD.

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Introduction to a Thematic Issue for WWOX

Cited by 15 publications

References 27 publications

Novel mutations in WWOX, RARS2, and C10orf2 genes in consanguineous Arab families with intellectual disability

Novel mutations in WWOX, RARS2, and C10orf2 genes in consanguineous Arab families with intellectual disability

Role of WW Domain-containing Oxidoreductase WWOX in Driving T Cell Acute Lymphoblastic Leukemia Maturation

Zfra restores memory deficits in Alzheimer's disease triple‐transgenic mice by blocking aggregation of TRAPPC6AΔ, SH3GLB2, tau, and amyloid β, and inflammatory NF‐κB activation

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