p53AIP1, a Potential Mediator of p53-Dependent Apoptosis, and Its Regulation by Ser-46-Phosphorylated p53

Oda, Katsutoshi; Arakawa, Hirofumi; Tanaka, Toshihiro; Matsuda, Koichi; Tanikawa, Chizu; Mori, Toshiki; Nishimori, Hiroyuki; Tamai, Katsuyuki; Tokino, Takashi; Nakamura, Yusuke; Taya, Yoichi

doi:10.1016/s0092-8674(00)00073-8

Cited by 1,088 publications

(962 citation statements)

References 39 publications

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“…In addition, transgelin interacts with p53 upregulating and stabilizing it (Figures 2A and 4). Phosphorylation of p53 at Ser46 is considered to be a primary determinant for the induction of apoptosis, by leading to selective transactivation of p53 target genes that have proapoptotic function [39]. We found that the introduction of transgelin results in the upregulation of phospho-p53 Ser46, which can induce apoptosis.…”

Section: Discussionmentioning

confidence: 78%

Transgelin induces apoptosis of human prostate LNCaP cells through its interaction with p53

Zhang¹,

Yang²,

Zheng³

et al. 2010

Asian J Androl

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The androgen receptor (AR) and its coregulators have important roles in the carcinogenesis of prostate cancer. p53 is an important tumour suppressor gene, and the absence of a fundamental p53 response may predispose to cancer. Transgelin, known as an ARA54-associated AR inhibitor, can suppress AR function in LNCaP cells. In addition to these effects, we aimed to elucidate the proapoptotic effects of the protein on LNCaP and its underlying mechanisms, especially the interaction between transgelin and p53. Cell counting, flow cytometric analysis and terminal deoxynucleotidyl transferase-dUTP nick-end labelling assays were applied to measure the proapoptotic effect of transgelin. Using western blotting of p53 and double immunofluorescence staining of p53 with transgelin, we show that transfection of transgelin results in increasing cytoplasmic translocation of p53 and upregulation of p53 expression. We also found an interaction between transgelin and p53 in vivo by mammalian two-hybrid and coimmunoprecipitation assays. The activation of the mitochondria-associated apoptosis pathway was observed in LNCaP cells after transfection with transgelin. These results are indicative of p53-mediated mitochondria-associated apoptotic effects of transgelin on LNCaP cells in addition to its known suppressive effects on the AR pathway.

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Section: Discussionmentioning

confidence: 78%

Transgelin induces apoptosis of human prostate LNCaP cells through its interaction with p53

Zhang¹,

Yang²,

Zheng³

et al. 2010

Asian J Androl

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show abstract

“…M, molecular weight marker; WT, wild type (p53 + / + ); N, nonischemic wild-type mice; 12 h, 12 h after ischemia; 24 h, 24 h after ischemia. p53 potentiates ischemic neuronal death I Yonekura et al ischemic stress may modify the protein into several active forms by phosphorylation, leading to a conformational change (Fuchs et al, 1995;Oda et al, 2000b;Koumenis et al, 2001;Latonen et al, 2001). Using antibodies against p53 phosphorylated at serines 18, 23, 37, 312, and 392 (kind gift from Dr Taya), we could not identify these forms (data not shown).…”

Section: Discussionmentioning

confidence: 91%

p53 Potentiates Hippocampal Neuronal Death Caused by Global Ischemia

Yonekura

Takai

Asai

et al. 2006

J Cereb Blood Flow Metab

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Although p53 controls cell death after various stresses, its role in neuronal death after brain ischemia is poorly understood. To address this issue, we subjected p53-deficient (p53 À/À and p53 + /-) mice (backcrossed for 12 generations with C57BL/6 mice) and wild-type mice (p53 + / + ) to transient global ischemia by the three-vessel occlusion method. Despite similar severity of ischemia, as shown by anoxic depolarization and cortical blood flow, neuronal death in the hippocampal cornus ammonis (CA)1 region was much more extensive in p53 + / + than in p53 À/À mice (surviving neuronal count, 9.3%63.0% versus 61.3%634.0% of nonischemic p53 + / + controls, respectively, P < 0.0037). In p53 + /À mice, a similar trend was also observed, though not statistically significant (43.5% of nonischemic p53 + / + controls). In p53 + / + mice, p53-like immunoreactivity in hippocampal CA1 neurons was enhanced at 12 h after ischemia, and messenger ribonucleic acid for Bax, a direct downstream target of p53, was also increased. These results indicate that p53 potentiates ischemic neuronal death in vivo and suggest that this molecule could be a therapeutic target in neuronal death after cerebral ischemia.

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“…For example, JNK has been proposed to modulate the release of pro-apoptotic factors from the mitochondrion (Fig. 5) and stabilizes the pro-apoptotic p53, which in term may impairs mitochondrial functions thorough the expression of p53AIP1 and a subsequent permeability transition [144]. On the contrary p53 might activate JNK via the MEKK4 involving the p53-mediated expression of the growth arrest and DNA damage-induced protein (GADD45) [201].…”

Section: Apoptosis Mitochondrial Function and Mapk Signal Transductionmentioning

confidence: 99%

MAPK signaling in neurodegeneration: influences of flavonoids and of nitric oxide

Schroeter

Boyd

Spencer

et al. 2002

Neurobiology of Aging

310

178

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Oxidative and nitrosative stress is increasingly associated with the pathology of neurodegeneration and aging. The molecular mechanisms underlying oxidative/nitrosative stress-induced neuronal damage are emerging and appear to involve a mode of death in which mitogen-activated protein kinase (MAPK) signaling pathways are strongly implicated. Thus, attention is turning towards the modulation of intracellular signaling as a therapeutic approach against neurodegeneration. Both endogenous and dietary agents have been suggested as potent modulators of intracellular signal transduction, e.g. nitric oxide and flavonoids, respectively. This review addresses recent findings on the biological effects of flavonoids and nitric oxide in neurodegeneration and aims to elucidate the rationale for their prospective use as modulators of cellular signal transduction. © 2002 Elsevier Science Inc. All rights reserved.Keywords: Apoptosis; Oxidative stress; Neuron; Flavonoids; MAP kinase; JNK; ERK; Epicatechin; Nitric oxide; Mitochondria; Redox status; Polyphenols Abbreviations: AKT, serine/threonine kinase (also known as protein kinase B); AP-1, activator protein-1; Apaf-1, apoptosis protease activating factor-1; ASK1, apoptosis signal-regulating kinase-1; Bad, Bcl-2/BclX Lassociated death promoting protein; Bax, pro-apoptotic protein of the Bcl-2 family; Bcl-2, B-cell lymphoma 2: protein with anti-apoptotic properties; BclX L , long form of Bclx: anti-apoptotic protein of the Bcl-2 family; Caspase, cysteinyl aspartic acid-protease; c-Jun, mammalian equivalent of Jun: part of the AP-1 transcription complex; CREB, cAMP response element binding protein; DIABLO/smac, mitochondria-related pro-apoptotic protein: inhibits XIAP; ERK1/2, extracellular signal-related kinase; Fas, CD95: member of the TNF receptor family; GSHST, glutathione Stransferase; JNK, c-Jun amino-terminal kinase; MAPK, mitogen-activated protein kinase; MAPKK, MAPK kinase; MAPKKK, MAPKK kinase; MEK1/2, ERK1/2-specific MAPKK; MKK4/7, JNK-specific MAPKK; MSK1, mitogen-and stress-activated kinase-1; NF-B, nuclear factor of immunoglobulin k locus in B-cells; ONOO − , peroxynitrite anion; p53, pro-apoptotic tumor suppressor gene product; PI3-kinase, phosphoinositol 3-kinase; Ras, small G-protein; RNS, reactive nitrogen species; ROS, reactive oxygen species; RSK, pp90 ribosomal S6 kinase; SAPK, stressactivated protein kinase; XIAP, X-linked inhibitor of apoptosis: inhibits the activation of caspase-9

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p53AIP1, a Potential Mediator of p53-Dependent Apoptosis, and Its Regulation by Ser-46-Phosphorylated p53

Cited by 1,088 publications

References 39 publications

Transgelin induces apoptosis of human prostate LNCaP cells through its interaction with p53

Transgelin induces apoptosis of human prostate LNCaP cells through its interaction with p53

p53 Potentiates Hippocampal Neuronal Death Caused by Global Ischemia

MAPK signaling in neurodegeneration: influences of flavonoids and of nitric oxide

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