Sh3rf2/POSHER Protein Promotes Cell Survival by Ring-mediated Proteasomal Degradation of the c-Jun N-terminal Kinase Scaffold POSH (Plenty of SH3s) Protein

Wilhelm, Michael; Kukekov, Nickolay V.; Schmit, Travis L.; Biagas, Katherine; Sproul, Andrew A.; Gire, Stephen; Maes, Margaret E.; Xu, Zhiheng; Greene, Lloyd A.

doi:10.1074/jbc.m111.269431

Cited by 28 publications

(35 citation statements)

References 29 publications

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“…A study reported that this gene was conserved, and widely and persistently expressed in mouse embryonic development, suggesting that the Prelid2 gene is involved in mouse embryonic development [Gao et al, 2009]. SH3RF2 encodes SH3 domain containing ring finger 2 protein that was found as a region‐specific molecular marker of nucleus accumbens of human brain [Wilhelm et al, 2012]. Sh3rg2 was demonstrated to promote cell survival by ring‐mediated proteasomal degradation of the c‐Jun N‐terminal kinase scaffold POSH (Plenty of SH3s) protein in many cell types [Wilhelm et al, 2012].…”

Section: Discussionmentioning

confidence: 99%

“…SH3RF2 encodes SH3 domain containing ring finger 2 protein that was found as a region‐specific molecular marker of nucleus accumbens of human brain [Wilhelm et al, 2012]. Sh3rg2 was demonstrated to promote cell survival by ring‐mediated proteasomal degradation of the c‐Jun N‐terminal kinase scaffold POSH (Plenty of SH3s) protein in many cell types [Wilhelm et al, 2012]. PLAC8L1 encodes placenta‐specific gene 8 protein (PLAC8)‐like 1 protein; however, its function is unclear.…”

Section: Discussionmentioning

confidence: 99%

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Identification of two inherited copy number variants in a male with autism supports two‐hit and compound heterozygosity models of autism

Gau

Liao

Hong

et al. 2012

American J of Med Genetics Pt B

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Autism is a childhood‐onset neurodevelopmental disorder with complex genetic mechanism underlying its etiology. Recent studies revealed that a few single de novo copy number variants of genomic DNA (copy number variants [CNVs]) are pathogenic and causal in some sporadic cases, adding support to the hypothesis that some sporadic autism might be caused by single rare mutation with large clinical effect. In this study, we report the detection of two novel private CNVs simultaneously in a male patient with autism. These two CNVs include a microduplication of ∼4.5 Mb at chromosome 4q12‐13.1 that was transmitted from his mother and a microdeletion of ∼1.8 Mb at 5q32 that was transmitted from his father. Several genes such as LPHN3, POU4F3, SH3RF2, and TCERG1 mapped to these two regions have psychiatric implications. However, the parents had only mild degree of attention deficit symptoms but did not demonstrate any obvious autistic symptoms or psychopathology. Our findings indicate that each of these two CNVs alone may not be pathogenic enough to cause clinical symptoms in their respective carriers, and hence they can be transmitted within each individual family. However, concomitant presence of these two CNVs might result in the clinical phenotypes of the affected patient reported here. Thus, our report of this family may represent an example to show that two hits of CNV and the presence of compound heterozygosity might be important mechanisms underlying the pathogenesis of autism. © 2012 Wiley Periodicals, Inc.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Identification of two inherited copy number variants in a male with autism supports two‐hit and compound heterozygosity models of autism

Gau

Liao

Hong

et al. 2012

American J of Med Genetics Pt B

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“…Similar to the immunostaining of cleaved caspase-3 post 2h H/R, cells were fixed with 4% paraformaldehyde. The level of apoptosis was determined using Click-iT TUNEL Alexa Fluor 488 Imaging Assay Kit from Life Technologies [33]. The green fluorescent image of TUNEL positive cells was digitally taken using a Zeiss Axiovert 135 microscope.…”

Section: Methodsmentioning

confidence: 99%

Modulation of p38 kinase by DUSP4 is important in regulating cardiovascular function under oxidative stress

Barajas-Espinosa

Basye

Angelos

2015

Free Radical Biology and Medicine

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Over-activation of p38 is implicated in many cardiovascular diseases (CVDs), including myocardial infarction, hypertrophy, heart failure, and ischemic heart disease. Numerous therapeutic interventions for CVDs have been directed towards the inhibition of the p38 mitogen-activated protein kinase activation that contributes to the detrimental effect after ischemia/reperfusion (I/R) injuries. However, the efficacy of these treatments is far from ideal as they lack specificity and are associated with high toxicity. Previously, we demonstrated that N-acetyl cysteine (NAC) pre-treatment up-regulates DUSP4 expression in endothelial cells, regulating p38 and ERK1/2 activities, thus providing a protective effect against oxidative stress. Here, endothelial cells under hypoxia/reoxygenation (H/R) insult and isolated heart I/R injury were used to investigate the role of DUSP4 on the modulation of the p38 pathway. In rat endothelial cells, DUSP4 is time-dependently degraded with H/R (0.25 ± 0.07 fold change of control after 2 h H/R). Its degradation is closely associated with hyper-phosphorylation of p38 (2.1 ± 0.36 fold change) and cell apoptosis, as indicated by the increase in cells immunopositive for cleaved caspase-3 (12.59% ± 3.38%) or TUNEL labeling (29.46% ± 3.75%). The inhibition of p38 kinase activity with 20 µM SB203580 during H/R prevents H/R-induced apoptosis, assessed via TUNEL (12.99% ± 1.89%). Conversely, DUSP4 gene silencing in endothelial cells augments their sensitivity to H/R-induced apoptosis (45.81% ± 5.23%). This sensitivity is diminished via the inhibition of p38 activity (total apoptotic cells drop to 17.47% ± 1.45%). Interestingly, DUSP4 gene silencing contributes to the increase in superoxide generation from cells. Isolated Langendorff-perfused mouse hearts were subjected to global I/R injury. DUSP4−/− hearts had significantly larger infarct size than WT. The increase in I/R-induced infarct in DUSP4−/− mice significantly correlates with reduced functional recovery (assessed by: RPP%, LVDP%, HR%, and dP/dtmax) as well as lower CF% and a higher initial LVEDP. From immunoblotting analysis, it is evident that p38 is significantly over-activated in DUSP4−/− mice after I/R injury. The activation of cleaved caspase-3 is seen in both WT and DUSP4−/− I/R hearts. Infusion of a p38 inhibitor prior to ischemia and during the reperfusion improves both WT and DUSP4−/− cardiac function. Therefore, the identification of p38 kinase modulation by DUSP4 provides a novel therapeutic target for oxidant-induced diseases, especially myocardial infarction.

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“…finger protein) family of proteins (Wilhelm et al, 2012) and contains three SH3 domains, as well as a Ring finger domain. We have previously shown that SH3RF2 promotes the survival of PC12 cells through the degradation of another SH3RF family member, POSH (SH3RF1) (Wilhelm et al, 2012). In addition, SH3RF2 is overexpressed in cancer cell lines and may function as an oncogene (Kim et al, 2014).…”

Section: (Legend Continued On Next Page)mentioning

confidence: 99%

Sh3rf2 Haploinsufficiency Leads to Unilateral Neuronal Development Deficits and Autistic-Like Behaviors in Mice

et al. 2018

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Sh3rf2/POSHER Protein Promotes Cell Survival by Ring-mediated Proteasomal Degradation of the c-Jun N-terminal Kinase Scaffold POSH (Plenty of SH3s) Protein

Cited by 28 publications

References 29 publications

Identification of two inherited copy number variants in a male with autism supports two‐hit and compound heterozygosity models of autism

Identification of two inherited copy number variants in a male with autism supports two‐hit and compound heterozygosity models of autism

Modulation of p38 kinase by DUSP4 is important in regulating cardiovascular function under oxidative stress

Sh3rf2 Haploinsufficiency Leads to Unilateral Neuronal Development Deficits and Autistic-Like Behaviors in Mice

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