p14ARF Triggers G2 Arrest Through ERK-Mediated Cdc25C Phosphorylation, Ubiquitination and Proteasomal Degradation

Eymin, Béatrice; Claverie, P.; Salon, Caroline; Brambilla, Christian; Brambilla, Élisabeth; Gazzéri, Sylvie

doi:10.4161/cc.5.7.2625

Cited by 49 publications

(42 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…5), suggesting that the UPS-dependent synaptophysin degradation is mediated by ERK activation. This is supported by several recent studies showing that the activation of the ERK pathway promoted the UPS-mediated degradation of the cell cycle protein Cdc25 (40,41) and the cell survival factor Bim (42). In the Drosophila eye, ERK signaling was shown to be required for the physiologic activity of Sina (seven in absentia), a key molecule for normal photoreceptor development (43).…”

Section: At1r-mediated Retinal Dysfunction In Diabetessupporting

confidence: 58%

Angiotensin II Type 1 Receptor Signaling Contributes to Synaptophysin Degradation and Neuronal Dysfunction in the Diabetic Retina

et al. 2008

View full text Add to dashboard Cite

OBJECTIVE-Pathogenic mechanisms underlying diabetesinduced retinal dysfunction are not fully understood. The aim of the present study was to show the relationship of the reninangiotensin system (RAS) with the synaptic vesicle protein synaptophysin and neuronal activity in the diabetic retina.RESEARCH DESIGN AND METHODS-C57BL/6 mice with streptozotocin-induced diabetes were treated with the angiotensin II type 1 receptor (AT1R) blocker telimsartan or valsartan, and retinal function was analyzed by electroretinography. Retinal production of the RAS components and phosphorylation of ERK (extracellular-signal regulated kinase) were examined by immunoblotting. Retinal mRNA and protein levels of synaptophysin were measured by quantitative RT-PCR and immunoblot analyses, respectively. In vitro, synaptophysin levels were also evaluated using angiotensin II-stimulated PC12D neuronal cells cultured with or without the inhibition of ERK signaling or the ubiquitin-proteasome system (UPS).RESULTS-Induction of diabetes led to a significant increase in retinal production of angiotensin II and AT1R together with ERK activation in the downstream of AT1R. AT1R blockade significantly reversed diabetes-induced electroretinography changes and reduction of synaptophysin protein, but not mRNA, levels in the diabetic retina. In agreement with the AT1R-mediated posttranscriptional downregulation of synaptophysin in vivo, in vitro application of angiotensin II to PC12D neuronal cells caused the UPS-mediated degradation of synaptophysin protein via AT1R, which proved to be induced by ERK activation.CONCLUSIONS-These data indicate the first molecular evidence of the RAS-induced synaptophysin degradation and neuronal dysfunction in the diabetic retina, suggesting the possibility of the AT1R blockade as a novel neuroprotective treatment for diabetic retinopathy.

show abstract

Section: At1r-mediated Retinal Dysfunction In Diabetessupporting

confidence: 58%

Angiotensin II Type 1 Receptor Signaling Contributes to Synaptophysin Degradation and Neuronal Dysfunction in the Diabetic Retina

et al. 2008

View full text Add to dashboard Cite

show abstract

“…There is contradictory evidence of a role for MAPK signaling in G 2 and mitosis in mammalian cells (5,6,8), but recent evidence suggests that some of this maybe attributed to cell lineage-dependent differences (44). MAPK signaling has also been implicated in the G 2 arrest associated with overexpression of BRCA1 and p14ARF, although these mechanisms involved Chk1, differentiating them from the present study (45,46).…”

Section: Discussioncontrasting

confidence: 56%

MAPK Pathway Activation Delays G2/M Progression by Destabilizing Cdc25B

Astuti

Pike

Widberg

et al. 2009

Journal of Biological Chemistry

View full text Add to dashboard Cite

“…Thus, the level within the signal transduction pathway, which is responsible for overstimulation, along with cell type may influence phenotypic outcome (see section II.B on ERKs). Furthermore, ERK also increases CDK inhibitor proteins p21, p27, and p53, among others, which results in cell cycle arrest (Smalley, 2003;Dhillon et al, 2007) and phosphorylation of CDC25c, leading to its ubiquitination and proteasomal degradation (Eymin et al, 2006), whereas Raf can also induce cell cycle arrest via p21 (Smalley, 2003). Thus, tumors must counteract this effect and can do so via AKT and RhoGTPase proteins (Dhillon et al, 2007).…”

Section: Mitogen-activated Protein Kinase and Cancer: An Overviewmentioning

confidence: 99%

“…In this scenario, MKP-1 expression could be deleterious. However, Ras overactivation, Raf, and ERK can induce cell cycle arrest (Hirakawa and Ruley, 1988;Smalley, 2003;Eymin et al, 2006;Dhillon et al, 2007). In this situation in which the neu oncogene correlates with MKP-1, phosphatase activity may reduce strong sustained ERK activity, favoring senescence or differentiation, which leads to sustained weak activity or transient ERK activity favoring proliferation (see sections II and V).…”

Section: A Breast Cancermentioning

confidence: 99%

Mitogen-Activated Protein (MAP) Kinase/MAP Kinase Phosphatase Regulation: Roles in Cell Growth, Death, and Cancer

Boutros

Chevet²,

Metrakos³

2008

Pharmacol Rev

510

448

View full text Add to dashboard Cite

p14ARF Triggers G2 Arrest Through ERK-Mediated Cdc25C Phosphorylation, Ubiquitination and Proteasomal Degradation

Cited by 49 publications

References 41 publications

Angiotensin II Type 1 Receptor Signaling Contributes to Synaptophysin Degradation and Neuronal Dysfunction in the Diabetic Retina

Angiotensin II Type 1 Receptor Signaling Contributes to Synaptophysin Degradation and Neuronal Dysfunction in the Diabetic Retina

MAPK Pathway Activation Delays G2/M Progression by Destabilizing Cdc25B

Mitogen-Activated Protein (MAP) Kinase/MAP Kinase Phosphatase Regulation: Roles in Cell Growth, Death, and Cancer

Contact Info

Product

Resources

About