Mechanisms of p53-induced apoptosis: in search of genes which are regulated during p53-mediated cell death

Choisy-Rossi, Caroline; Reisdorf, Philippe; Yonish-Rouach, Elisheva

doi:10.1016/s0378-4274(98)00238-0

Cited by 33 publications

(18 citation statements)

References 32 publications

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“…The tumour suppressor, p53, is involved in essential functions such as DNA repair, transcription, genomic stability, senescence, cell cycle control and apoptosis [263]. Hsp27 is one of the target genes of p53 and p53-dependent induction of Hsp27 expression has been observed [264].…”

Section: Silencing αB-crystallin Sensitized Arpe-19 Cells To Methyl Gmentioning

confidence: 99%

Small heat shock proteins: Role in cellular functions and pathology

Raman

Tangirala

Rao

2015

Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics

393

321

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Small heat shock proteins (sHsps) are conserved across species and are important in stress tolerance. Many sHsps exhibit chaperone-like activity in preventing aggregation of target proteins, keeping them in a folding-competent state and refolding them by themselves or in concert with other ATP-dependent chaperones. Mutations in human sHsps result in myopathies, neuropathies and cataract. Their expression is modulated in diseases such as Alzheimer's, Parkinson's and cancer. Their ability to bind Cu2+, and suppress generation of reactive oxygen species (ROS) may have implications in Cu2+-homeostasis and neurodegenerative diseases. Circulating αB-crystallin and Hsp27 in the plasma may exhibit immunomodulatory and anti-inflammatory functions. αB-crystallin and Hsp20 exhitbit anti-platelet aggregation: these beneficial effects indicate their use as potential therapeutic agents. sHsps have roles in differentiation, proteasomal degradation, autophagy and development. sHsps exhibit a robust anti-apoptotic property, involving several stages of mitochondrial-mediated, extrinsic apoptotic as well as pro-survival pathways. Dynamic N- and C-termini and oligomeric assemblies of αB-crystallin and Hsp27 are important factors for their functions. We propose a "dynamic partitioning hypothesis" for the promiscuous interactions and pleotropic functions exhibited by sHsps. Stress tolerance and anti-apoptotic properties of sHsps have both beneficial and deleterious consequences in human health and diseases. Conditional and targeted modulation of their expression and/or activity could be used as strategies in treating several human disorders. The review attempts to provide a critical overview of sHsps and their divergent roles in cellular processes particularly in the context of human health and disease.

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Section: Silencing αB-crystallin Sensitized Arpe-19 Cells To Methyl Gmentioning

confidence: 99%

Small heat shock proteins: Role in cellular functions and pathology

Raman

Tangirala

Rao

2015

Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics

393

321

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“…4A). [18][19][20] After exposure to gemcitabine, we observed that MA + cells displayed a significantly higher increase of p21 and PUMA mRNA expression levels than MP or MAcells (+30 μ and +70%, p < 0.05). MA -cells had a significantly lower increase of p21 after exposure to gemcitabine as compared to MP cells (p < 0.05, -40%).…”

Section: Introductionmentioning

confidence: 99%

Expression of Arl2 is associated with p53 localization and chemosensitivity in a breast cancer cell line

Béghin

Matera²,

Brunet-Manquat³

et al. 2008

Cell Cycle

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In mammalian cells, ADP ribosylation factor like 2 (Arl2) has been shown to form a complex with tubulin binding cofactor D (TBC-D) and the tumor suppressor protein phosphatase 2A (PP2A). We have previously shown that alterations in Arl2 protein content were associated with corresponding modifications of the tumor suppressor PP2Ac protein content in breast cancer cells. Here, we show that modified Arl2 expression level influences sensitivity to various anticancer compounds such as taxol, navelbine, gemcitabine and doxorubicin in MCF7 derived cell lines. Modifications of Arl2 expression levels were also associated with an altered phosphorylation status and/or cellular sublocalization of certain PP2A targets such as p53, a key mediator of chemotherapy-induced apoptosis. A decreased level of Arl2 expression was associated with an increase of phospho-ser15-p53, a form which was found to be preferentially bound to microtubules. Assays using okadaic and cantharidic acid, two different PP2A inhibitors, showed an increase in microtubule-bound phospho-p53 and reduced sensitivity to chemotherapy. Our results suggest that Arl2 could, via PP2A, influence p53 phosphorylation status. Certain forms of phosphorylated p53 demonstrating increased binding to microtubules appear to be less prone to nuclear translocation after exposure to chemotherapeutic agents, thereby possibly contributing to reduced chemosensitivity.

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“…On the other hand, p53-dependent apoptotic signals are not well characterized. Although it has been suggested that the apoptotic mechanism of p53 requires bax activation (Choisy-Rossi et al, 1998), bax is dispensable for p53-dependent apoptosis in g-irradiated thymocytes (Knudson et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

P53 mediates ceramide-induced apoptosis in SKN-SH cells

et al. 2002

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Ceramide induces apoptotic cell death in a dose-and time-dependent manner in neuroblastoma SKN-SH cells. Pretreatment with caspase inhibitors blocks cell death, suggesting that a set of caspase activities including caspase 1, as well as caspase 3, are involved in ceramideinduced apoptosis in SKN-SH cells. Treatment with a caspase inhibitor 3 h after ceramide addition did not inhibit cell death, although caspase activity was substantially reduced. Ceramide-induced apoptosis is accompanied by accumulation of p53 followed by an increase of Bax and decrease of Bcl-2 levels. Inhibition of p53 expression with p53 antisense oligonucleotides inhibits apoptosis and prevents the increase in Bax and decrease in Bcl-2. Furthermore, pretreatment with p53 antisense oligonucleotides markedly inhibits the induction of caspase activity. These results suggest that p53 regulates the ratio Bcl-2/Bax and the expression/ activation of caspases during ceramide-induced apoptosis in SKN-SH cells. Caspase inhibition did not alter the expression of p53, Bcl-2 and Bax. Thus ceramideinduced reduction in the Bcl-2/Bax ratio, increase in caspase activity, and apoptosis is dependent upon increases in cellular p53 levels which play a critical role in the regulation of apoptotic cell death.

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Mechanisms of p53-induced apoptosis: in search of genes which are regulated during p53-mediated cell death

Cited by 33 publications

References 32 publications

Small heat shock proteins: Role in cellular functions and pathology

Small heat shock proteins: Role in cellular functions and pathology

Expression of Arl2 is associated with p53 localization and chemosensitivity in a breast cancer cell line

P53 mediates ceramide-induced apoptosis in SKN-SH cells

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