JNK promotes Bax translocation to mitochondria through phosphorylation of 14-3-3 proteins

Tsuruta, Fuminori; Sunayama, Jun; Mori, Yasunori; Hattori, Satoshi; Shimizu, Shigeomi; Tsujimoto, Yoshihide; Yoshioka, Katsuji; Masuyama, Norihisa; Gotoh, Yukiko

doi:10.1038/sj.emboj.7600194

Cited by 510 publications

(387 citation statements)

References 61 publications

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“…Several studies suggested that the estrogen and leptin systems are related via functional cross talk. For example, estrogens have been shown to regulate the expression of leptin (Casabiell et al, 1998;Tsuruta et al, 2004) and its receptor (Bennett et al, 1998) in adipose tissue and brain, respectively. Reciprocally, leptin stimulates ovarian cancer cell growth involving ERα transcriptional activation via the STAT-3 signaling pathways (Choi et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Withdrawal of dietary phytoestrogens in adult male rats affects hypothalamic regulation of food intake, induces obesity and alters glucose metabolism

Andreoli

Stoker

Rossetti

et al. 2015

Molecular and Cellular Endocrinology

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A B S T R A C TThe absence of phytoestrogens in the diet during pregnancy has been reported to result in obesity later in adulthood. We investigated whether phytoestrogen withdrawal in adult life could alter the hypothalamic signals that regulate food intake and affect body weight and glucose homeostasis.Male Wistar rats fed from conception to adulthood with a high phytoestrogen diet were submitted to phytoestrogen withdrawal by feeding a low phytoestrogen diet, or a high phytoestrogen-high fat diet. Withdrawal of dietary phytoestrogens increased body weight, adiposity and energy intake through an orexigenic hypothalamic response characterized by upregulation of AGRP and downregulation of POMC. This was associated with elevated leptin and T4, reduced TSH, testosterone and estradiol, and diminished hypothalamic ERα expression, concomitant with alterations in glucose tolerance.Removing dietary phytoestrogens caused manifestations of obesity and diabetes that were more pronounced than those induced by the high phytoestrogen-high fat diet intake.

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Section: Discussionmentioning

confidence: 99%

Withdrawal of dietary phytoestrogens in adult male rats affects hypothalamic regulation of food intake, induces obesity and alters glucose metabolism

Andreoli

Stoker

Rossetti

et al. 2015

Molecular and Cellular Endocrinology

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“…In concert with these results, the Thr735 kinase TTK-phosphorylated c-Abl to be sequestered in the cytoplasm in the unstressed condition. However, upon exposure to genotoxic stress, 14-3-3 is rapidly phosphorylated by c-Jun N-terminal kinase and presumably modified its tertiary structure, thus rendering it dissociation from target molecules (Tsuruta et al, 2004). This dissociation is independent on the phosphorylation in target molecules, such as c-Abl at Thr735.…”

Section: Discussionmentioning

confidence: 99%

TTK/Mps1 controls nuclear targeting of c-Abl by 14-3-3-coupled phosphorylation in response to oxidative stress

et al. 2008

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Upon exposure to genotoxic stress, the c-Abl tyrosine kinase is released from cytoplasmic 14-3-3 proteins and then is targeted to the nucleus. Phosphorylation of Thr735 in c-Abl is critical for binding to 14-3-3; however, kinases responsible for this phosphorylation are unknown. Here, we identify CLK1, CLK4, MST1, MST2 and TTK (also known as Mps1) as novel Thr735 kinases in vitro by expression cloning strategy using phosphospecific antibody. We also demonstrate that ectopic expression of these kinases is capable for phosphorylation of Thr735 in cells. Importantly, upon exposure to oxidative stress, phosphorylation of Thr735 is transiently upregulated, and the status of this phosphorylation remains unchanged in cells silenced for CLK1, CLK4, MST1 or MST2. By contrast, knockdown of TTK attenuates phosphorylation of Thr735, suggesting that TTK is a physiological kinase that phosphorylates Thr735. In concert with these results, we show that, in cells silenced for TTK, c-Abl is accumulated in the nucleus even in unstressed condition and no further targeting into the nucleus occurs after oxidative stress. Moreover, nuclear entrapment of c-Abl by knocking down TTK enhances oxidative stress-induced apoptosis. These findings provide evidence that TTK phosphorylates c-Abl at Thr735 and that this phosphorylation is of importance to the cytoplasmic sequestration of c-Abl.

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“…Bad with 14-3-3 (Zha et al, 1996), Bim (Puthalakath et al, 1999;Chen and Zhou, 2004) and Bmf with the cytoskeleton (Puthalakath et al, 2001), and recently Bax with the scaffolding protein 14-3-3 (Nomura et al, 2003;Tsuruta et al, 2004). Studies to identify this 96 kDa protein complex are ongoing.…”

Section: Discussionmentioning

confidence: 99%

Differential Profile of Nix Upregulation and Translocation during Hypoxia/Ischaemia in Vivo Versus in Vitro

Birse-Archbold

Kerr

Jones

et al. 2005

J Cereb Blood Flow Metab

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Nix, a hypoxia-sensitive member of the Bcl-2 family, is upregulated at the mRNA level during hypoxia through induction of a hypoxia-inducible factor-1a (HIF-1a) response element in its promoter sequence. However, the mechanism(s) regulating Nix protein activation remain unclear. The present studies examine Nix protein expression and subcellular distribution in response to hypoxic stimuli in vivo and in culture and to two disparate apoptotic stimuli in vitro. Upregulation and translocation of Nix (by day 5) in hypoxic/serum-deprived CHO-K1 cells, was preceded by Bax activation (by day 4) and caspase-3 processing (by day 2), suggesting that initiation of cell death in vitro is a Nixindependent event. In contrast, an early Nix response (upregulation and translocation to the mitochondria) was observed after 6 h of middle cerebral artery occlusion in the rat. Nix translocation was observed in the ipsilateral cortex and striatum before other histological (infarct development, neuronal loss, apoptotic body formation) or biochemical (Bax activation or caspase-3 cleavage) markers of damage were detected. While fundamental differences between hypoxia/ischaemia in culture and in vivo likely explain the different temporal profiles of Nix, Bax, and caspase-3 activation observed, these studies show that like Bax, mitochondrial accumulation is a common event during Nix activation. These are the first studies to show upregulation and translocation of Nix in the ischaemic brain and suggest Nix to be a novel therapeutic target in ischaemic research. Moreover, Nix upregulation in staurosporine-treated SH-SY5Y cells and dexamethasone-treated A1.1 cells supports a more generalized role for Nix in apoptotic cell death.

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JNK promotes Bax translocation to mitochondria through phosphorylation of 14-3-3 proteins

Cited by 510 publications

References 61 publications

Withdrawal of dietary phytoestrogens in adult male rats affects hypothalamic regulation of food intake, induces obesity and alters glucose metabolism

Withdrawal of dietary phytoestrogens in adult male rats affects hypothalamic regulation of food intake, induces obesity and alters glucose metabolism

TTK/Mps1 controls nuclear targeting of c-Abl by 14-3-3-coupled phosphorylation in response to oxidative stress

Differential Profile of Nix Upregulation and Translocation during Hypoxia/Ischaemia in Vivo Versus in Vitro

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