p53-Induced Apoptosis as a Safeguard against Cancer

Asker, Charlotte; Wiman, Klas G.; Selivanova, Galina

doi:10.1006/bbrc.1999.1446

Cited by 77 publications

(51 citation statements)

References 78 publications

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“…These downstream effectors have been characterized with respect to p53-mediated growth arrest, 17 but the pathways associated with p53-mediated apoptosis remain obscure. 18 In addition to its transcriptional transactivating activity, p53 may promote apoptosis by repressing the expression of select genes. 19,20 This particular action of p53 is not well understood, but it does not appear to depend on the presence of p53 consensus binding sites in the promoter region of repressed genes.…”

Section: The P53 Genementioning

confidence: 99%

“…However, the precise mechanism underlying the involvement of GAPDH in neuronal apoptosis is unclear. Other genes, such as DR5, Fas, Fas ligand 18 and PERP 149 have been shown to be induced by apoptotic stimuli as a result of p53 activation in a variety of non-neuronal cell types, but the involvement of these genes in p53-dependent neuronal apoptosis is not known.…”

Section: Mechanism Of P53-mediated Cell Death In Neuronsmentioning

confidence: 99%

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The role of p53 in neuronal cell death

2000

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The p53 tumor suppressor gene is a sequence-specific transcription factor that activates the expression of genes engaged in promoting growth arrest or cell death in response to genotoxic stress. A possible role for p53-related modulation of neuronal viability has been suggested by the finding that p53 expression is elevated in damaged neurons in acute models of injury such as ischemia and epilepsy and in brain tissue samples derived from patients with chronic neurodegenerative diseases. Moreover, the absence of p53 has been shown to protect neurons from a wide variety of acute toxic insults. Signal transduction pathways associated with p53-induced cell death are being unraveled and suggest that intervention may prove fruitful in maintaining neuronal viability and restoring function following cytopathic insults.

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Section: The P53 Genementioning

confidence: 99%

Section: Mechanism Of P53-mediated Cell Death In Neuronsmentioning

confidence: 99%

The role of p53 in neuronal cell death

2000

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“…Thus, the anti-tumorigenic effect of p53 is abrogated in HPV-positive cell lines (Haffner and Oren, 1995). However, several studies clearly demonstrate that p53 activities are not completely eliminated in E6-expressing cells and that HPV-infected cervical epithelial cells still contain residual transcriptionally active p53, that can lead to cell cycle arrest and/or apoptosis (Asker et al, 1999;Butz et al, 1995Butz et al, , 1996Hietanen et al, 2000). The induction of apoptosis by p53 is complex and not yet understood in detail; it involves transcriptional activation of a variety of downstream target genes such as, p21 WAF1 , Bax (reviewed by Sheikh and Fornace, 2000), and probably transcription-independent events as well (Gottlieb and Oren, 1998).…”

Section: Introductionmentioning

confidence: 99%

Human papillomaviruses type 16+ and 18+ cervical carcinoma cells are sensitive to staurosporine‐mediated apoptosis

Bernard¹,

Prétet²,

Charlot³

et al. 2003

Biology of the Cell

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We have recently shown that staurosporine (ST) can trigger apoptosis of CaSki and HeLa cervical tumor cells from G2/M checkpoint, though the mechanism remains elusive. In this study, we reported that ST induced the inhibition of E6 and E7 viral oncogene and MDM2 expression, while it led to increased levels of p53, which was transiently located to mitochondria. Additionally, the proteins of the p53-regulated genes, p21 WAF1 and Bax, were increased with a similar time, while Bcl-2 and Bcl-X L expression was lowered. Upon ST treatment, the cytochrome c was released into the cytosol and, then, activation of caspases-9 and -3 led to Poly(ADP)RibosePolymerase (PARP) cleavage. Finally, characteristic morphological signs confirmed the apoptosis execution. Thus, taken together, all these observations suggest that apoptosis can be reactivated in HPV-positive human carcinoma cells and highlight that ST could be used as a potently chemotherapy agent to enhance the sensitivity of tumor cells to apoptosis.

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“…ecological stress | evolution | Apaf1 | Noxa | Puma T he regulatory mechanisms of p53 mutation related to tumorigenesis have been widely studied and elucidated (1,2). Notably, however, p53 evolution and adaptation to environmental stresses have not attracted as much attention.…”

mentioning

confidence: 99%

Codon 104 variation of p53 gene provides adaptive apoptotic responses to extreme environments in mammals of the Tibet plateau

Zhao

Wang

Zhang

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Mutational changes in p53 correlate well with tumorigenesis. Remarkably, however, relatively little is known about the role that p53 variations may play in environmental adaptation. Here we report that codon asparagine-104 (104N) and glutamic acid-104 (104E), respectively, of the p53 gene in the wild zokor (Myospalax baileyi) and root vole (Microtus oeconomus) are adaptively variable, meeting the environmental stresses of the Tibetan plateau. They differ from serine-104 (104S) seen in other rodents, including the lowland subterranean zokor Myospalax cansus, and from serine 106 (106S) in humans. Based on site-directed mutational analysis in human cell lines, the codon 104N variation in M. baileyi is responsible for the adaptive balance of the transactivation of apoptotic genes under hypoxia, cold, and acidic stresses. The 104E p53 variant in Microtus oeconomus suppresses apoptotic gene transactivation and cell apoptosis. Neither 104N nor 104E affects the cell-cycle genes. We propose that these variations in p53 codon 104 are an outcome of environmental adaptation and evolutionary selection that enhance cellular strategies for surviving the environmental stresses of hypoxia and cold (in M. baileyi and M. oeconomus) and hypercapnia (in M. baileyi) in the stressful environments of the Qinghai-Tibet plateau.T he regulatory mechanisms of p53 mutation related to tumorigenesis have been widely studied and elucidated (1, 2). Notably, however, p53 evolution and adaptation to environmental stresses have not attracted as much attention. Current studies show that p53 is a master sensor and regulator in response to various stressors, such as DNA damage and hypoxia (3-6). Activation of p53 by stresses results in cell-cycle arrest, DNA repair, senescence, or apoptosis in which a series of p53 target genes are involved to maintain genomic integrity (2). The p53 variations associated with environmental stresses have been described in the Mexican salamander axolotl Ambystoma mexicanum and the Israeli blind subterranean mole rat (Spalax judaei; hereafter, S.j.) (7-9).For animals existing on high plateaus, hypoxia and cold serve as strong environmental selective pressures generating adaptive complexes to cope with these stresses. Animals that have evolved on plateaus adopt various strategies involving multiple variations to regulate a series of genes (3, 7). The zokor (Myospalax baileyi, Thomas, 1911; hereafter M.b.) and root vole (Microtus oeconomus, Pallas, 1776; hereafter M.o.) are the dominant native mammals living on the alpine meadow of the Qinghai-Tibet Plateau of China at altitudes of 3,000-4,500 m (equivalent to 11.0-13.0% O 2 at sea level). M.b. is genetically close to Myospalax cansus (Lyon, 1907; hereafter, M.c.), which lives in subterranean burrows at a lower altitude of about 800 m in the lowland of western China. M.b. and M.c. spend their entire life cycle at 70-250 cm underground with significantly low O 2 and high CO 2 levels in their burrows (10). Since the collision of the Indian and the Eurasian plates during the...

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p53-Induced Apoptosis as a Safeguard against Cancer

Cited by 77 publications

References 78 publications

The role of p53 in neuronal cell death

The role of p53 in neuronal cell death

Human papillomaviruses type 16+ and 18+ cervical carcinoma cells are sensitive to staurosporine‐mediated apoptosis

Codon 104 variation of p53 gene provides adaptive apoptotic responses to extreme environments in mammals of the Tibet plateau

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