Regulation of p53 Translation and Induction after DNA Damage by Ribosomal Protein L26 and Nucleolin

Takagi, Motoki; Absalon, Michael J.; McLure, Kevin G.; Kastan, Michael B.

doi:10.1016/j.cell.2005.07.034

Cited by 606 publications

(681 citation statements)

References 55 publications

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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%

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%

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

et al. 2006

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“…We first investigated several reported candidate mRNAs, including BcL-xL, TNF-a,GADD45a, HOXA2, IER3 and p53 (Iervolino et al, 2002;Takagi et al, 2005;Yugami et al, 2007). Among them, only Bcl-xL and TNF-a cytosolic mRNA were found to be decreased on ActD treatment (data not shown).…”

Section: B23 Binds To Hnrnpu and Hnrnpa1 In The Cytosol In Response Tmentioning

confidence: 99%

B23 acts as a nucleolar stress sensor and promotes cell survival through its dynamic interaction with hnRNPU and hnRNPA1

et al. 2010

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“…These interactions suppress Mdm2 E3 ligase activity against the degradation of p53 protein. Moreover, rpL26 was identified as a p53 translational activator as it can bind the 5 0 -UTR of p53 mRNA and increase translation (Takagi et al, 2005). In contrast to the above described ribosomal proteins, there is another association between ribosomal protein (rpL26) and Mdm2 that differently regulates p53 protein level.…”

Section: Introductionmentioning

confidence: 99%

Aberrant ribosome biogenesis activates c-Myc and ASK1 pathways resulting in p53-dependent G1 arrest

2011

Oncogene

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The largest energy consumer in the cell is the ribosome biogenesis whose aberrancy elicits various diseases in humans. It has been recently revealed that p53 induction, along with cell cycle arrest, is related with abnormal ribosome biogenesis, but the exact mechanism still remains unknown. In this study, we have found that aberrant ribosome biogenesis activates two parallel cellular pathways, c-Myc and ASK1/p38, which result in p53 induction and G1 arrest. The c-Myc stabilizes p53 by rpL11-mediated HDM2 inhibition, and ASK1/p38 activates p53 by phosphorylation on serine 15 and 33. Our studies demonstrate the relationship between these two pathways and p53 induction. The changes caused by impaired ribosomal stress, such as p53 induction and G1 arrest, were completely disappeared by inhibition of either pathway. These findings suggest a monitoring mechanism of c-Myc and ASK1/p38 against abnormal ribosome biogenesis through controlling the stability and activity of p53 protein.

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Regulation of p53 Translation and Induction after DNA Damage by Ribosomal Protein L26 and Nucleolin

Cited by 606 publications

References 55 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

B23 acts as a nucleolar stress sensor and promotes cell survival through its dynamic interaction with hnRNPU and hnRNPA1

Aberrant ribosome biogenesis activates c-Myc and ASK1 pathways resulting in p53-dependent G1 arrest

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