Negative feedback regulation of wild-type p53 biosynthesis

Mosner, J; Bauer, Christian; Deppert, Wolfgang

doi:10.1007/bf02572252

Cited by 106 publications

(172 citation statements)

References 31 publications

(43 reference statements)

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“…This is different from what we observe in mammalian cells but it well illustrates how cell-typespecific factors tightly control translation of the p53 message. It has also been reported that p53 itself can mediate control of its own synthesis through interaction with its 5 0 UTR (Mosner et al, 1995) and a recent publication reports that the 5 0 UTR is responsible for mediating translation control of p53 after g-irradiation (Takagi et al, 2005). This could indicate that regions within the coding domain as well as within the 5 0 UTR mediate different types of stress-dependent translation control of p53 synthesis.…”

Section: Discussionmentioning

confidence: 96%

“…However, it has been demonstrated in both human, mouse and yeast models that the UTRs of p53 can mediate control of its translation (Mosner et al, 1995;Fu et al, 1999;Mokdad-Gargouri et al, 2001). We therefore addressed the putative role of the mRNA sequence flanking the 5 0 end of the p53 encoding sequence in controlling p53/47 synthesis.…”

Section: Expression Of P53 and P53/47mentioning

confidence: 99%

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Expression of p53 and p53/47 are controlled by alternative mechanisms of messenger RNA translation initiation

et al. 2006

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P53 controls the growth and survival of cells by acting in response to a multitude of cellular stresses. It is, however, not yet fully understood how different p53 activation pathways result in either cell cycle arrest or apoptosis. We and others have described an N-terminally truncated p53 protein (p53/47) originating from a second translation initiation site in the p53 messenger RNA (mRNA), which can interact with p53 and impose altered stability and transactivation properties to p53 complexes. Here we show that cap-dependent and cap-independent mechanisms of initiation govern the translation of the p53 mRNA. Changes in synthesis of full-length p53 or p53/47 are regulated through distinct cell stress-induced pathways acting through separate regions of the p53 mRNA. We also show that some cytotoxic drugs require the presence of full-length p53 to induce apoptosis, whereas for others p53/47 is sufficient. This indicates that by harbouring alternative translation initiation sites, the p53 mRNA gives rise to different levels of the p53 isoforms which help to orchestrate the cell biological outcome of p53 activation in response to different types of cell stress. This sheds new light into the way p53 can integrate and differentiate a large multiplicity of changes in the cellular environment.

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Section: Discussionmentioning

confidence: 96%

Section: Expression Of P53 and P53/47mentioning

confidence: 99%

Expression of p53 and p53/47 are controlled by alternative mechanisms of messenger RNA translation initiation

et al. 2006

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“…Auto-regulation is an important model of translational regulation for proteins. The binding sites of proteins on its own mRNA could locate on the regions of 5 0 UTR, coding region or 3 0 UTR [10,25]. For example, p53 protein of murine and human could bind to the 5 0 UTR or 3 0 UTR on its own mRNA [10].…”

Section: Discussionmentioning

confidence: 99%

“…The binding sites of proteins on its own mRNA could locate on the regions of 5 0 UTR, coding region or 3 0 UTR [10,25]. For example, p53 protein of murine and human could bind to the 5 0 UTR or 3 0 UTR on its own mRNA [10]. In the present study, we confirmed that there also exist an interaction between p53 protein and its cognate mRNA in zebrafish embryos, and the binding site is located on the 3 0 UTR region.…”

Section: Discussionmentioning

confidence: 99%

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Zebrafish p53 protein enhances the translation of its own mRNA in response to UV irradiation and CPT treatment

Zhao

Ding

et al. 2012

FEBS Letters

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Edited by Varda RotterKeywords: p53 Zebrafish RNA binding protein Translational regulation a b s t r a c t p53 protein is an important regulatory factor involved in cell growth and development. In our previous study, we demonstrated that recombined zebrafish p53 protein could specifically bind to its own mRNA in vitro. To determine if a similar interaction exists in zebrafish and if this interaction affects zebrafish development, in the present study, we investigated the interaction of p53 protein and its mRNA in zebrafish embryos. Our results revealed that expressed zebrafish p53 protein could bind with its own mRNA in zebrafish embryos. Furthermore, the endogenous activated or ectopically expressed p53 protein could enhance the relative activity of Renilla luciferase fused with p53 3 0 UTR in response to UV irradiation and CPT treatment, and retarded development of zebrafish embryos was observed.

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Why is p53 protein stabilized in neoplasia? Some answers but many more questions!

1998

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Negative feedback regulation of wild-type p53 biosynthesis

Cited by 106 publications

References 31 publications

Expression of p53 and p53/47 are controlled by alternative mechanisms of messenger RNA translation initiation

Expression of p53 and p53/47 are controlled by alternative mechanisms of messenger RNA translation initiation

Zebrafish p53 protein enhances the translation of its own mRNA in response to UV irradiation and CPT treatment

Why is p53 protein stabilized in neoplasia? Some answers but many more questions!

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