Regulation of apoptosis signal‐regulating kinase 1 degradation by Gα13

Kutuzov, Mikhail A.; Андреева, А. В.; Voyno-Yasenetskaya, Tatyana A.

doi:10.1096/fj.06-8029com

Cited by 13 publications

(10 citation statements)

References 45 publications

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“…Interestingly, the processes leading to this suppression in vitro appear at first glance to differ from those occurring in the more complex environment in vivo ; however recent studies have revealed that many of the protein interactions affecting ASK1 activation are also involved in regulating its expression levels in the cell (He et al , 2006; Hwang et al , 2005; Kutuzov et al , 2007; Liu and Min, 2002). Therefore, it is conceivable that effects of minocycline in vitro and in vivo share a common mechanism that simply manifests differently in short-term cell culture as compared to several weeks in the brain in vivo .…”

Section: Discussionmentioning

confidence: 99%

Mechanisms of minocycline-induced suppression of simian immunodeficiency virus encephalitis: inhibition of apoptosis signal-regulating kinase 1

2008

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Human immunodeficiency virus (HIV) infection of the central nervous system (CNS) can lead to cognitive dysfunction, even in individuals treated with highly active antiretroviral therapy. Using an established simian immunodeficiency virus (SIV)/macaque model of HIV CNS disease, we previously reported that infection shifts the balance of activation of mitogen-activated protein kinase (MAPK) signaling pathways in the brain, resulting in increased activation of the neurodegenerative MAPKs p38 and JNK. Minocycline treatment of SIV-infected macaques reduced the incidence and severity of SIV encephalitis in this model, and suppressed the activation of p38 in the brain. The purpose of this study was to further examine the effects of minocycline on neurodegenerative MAPK signaling. We first demonstrated that minocycline also decreases JNK activation in the brain and levels of the inflammatory mediator nitric oxide (NO). We next used NO to activate these MAPK pathways in vitro, and demonstrated that minocycline suppresses p38 and JNK activation by reducing intracellular levels, and hence, activation of apoptosis signal-regulating kinase 1 (ASK1), a MAPKKK capable of selectively activating both pathways. We then demonstrated that ASK1 activation in the brain during SIV infection is suppressed by minocycline. By suppressing p38 and JNK activation pathways, which are important for the production of and responses to inflammatory mediators, minocycline may interrupt the vicious cycle of inflammation that both results from, and promotes, virus replication in SIV and HIV CNS disease.

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Section: Discussionmentioning

confidence: 99%

Mechanisms of minocycline-induced suppression of simian immunodeficiency virus encephalitis: inhibition of apoptosis signal-regulating kinase 1

2008

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“…The apoptosis in this model was blocked by the co-transfection of dominant negative Ask1. Recent evidence suggests that activated Gα 13 may also increase Ask1 expression by reducing its ubiquitination and subsequent degradation [108]. Additionally, overexpression of this truncated Gα 13 stimulated apoptosis in Rat 1A fibroblasts through JNK signaling (Table 4, Row 4).…”

Section: Review Of Literature On G Protein Regulation Of Apoptosismentioning

confidence: 99%

Heterotrimeric G Proteins and Apoptosis: Intersecting Signaling Pathways Leading to Context Dependent Phenotypes

Yanamadala¹,

Negoro²,

Denker³

2009

CMM

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Apoptosis, a programmed cell death mechanism, is a fundamental process during the normal development and somatic maintenance of all multicellular organisms and thus is highly conserved and tightly regulated through numerous signaling pathways. Apoptosis is of particular clinical importance as its dysregulation contributes significantly to numerous human diseases, primarily through changes in the expression and activation of key apoptotic regulators. Each of the four families of heterotrimeric G proteins (Gs, Gi/o, Gq/11 and G12/13) has been implicated in numerous cellular signaling processes, including proliferation, transformation, migration, differentiation, and apoptosis. Heterotrimeric G protein signaling is an important but not widely studied mechanism regulating apoptosis. G protein Signaling and Apoptosis broadly cover two large bodies of literature and share numerous signaling pathways. Examination of the intersection between these two areas is the focus of this review. Several studies have implicated signaling through each of the four heterotrimeric G protein families to regulate apoptosis within numerous disease contexts, but the mechanism(s) are not well defined. Each G protein family has been shown to stimulate and/or inhibit apoptosis in a context-dependent fashion through regulating numerous downstream effectors including the Bcl-2 family, NF-κB, PI3 Kinase, MAP Kinases, and small GTPases. These cell-type specific and G protein coupled receptor dependent effects have led to a complex body of literature of G protein regulation of apoptosis. Here, we review the literature and summarize apoptotic signaling through each of the four heterotrimeric G protein families (and the relevant G protein coupled receptors), and discuss limitations and future directions for research on regulating apoptosis through G protein coupled mechanisms. Continued investigation in this field is essential for the identification of important targets for pharmacological intervention in numerous diseases.

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“…In neuroblastoma cells, expression of 5‐HT 4 (a) receptors causes RhoA‐dependent neurite retraction and cell rounding both under basal conditions and after agonist stimulation, suggesting that by activating 5‐HT 4 (a) receptor G α 13 pathway, 5‐HT plays a prominent role in regulating neuronal architecture 109. Short‐term activation of 5‐HT 4 R coupled to G α 13 increases apoptosis signal‐regulating kinase (ASK1) expression, whereas prolonged activation down regulates both G α 13 and ASK1 111. In gonadotropin‐releasing hormone neurons, selective activation of 5‐HT 4 R stimulate cAMP production, increase their firing rate and cause a sustained and robust increase in GnRH release 108,112.…”

Section: ‐Ht4 Receptormentioning

confidence: 99%