Mazan-Mamczarz, K. et al. RNA-binding protein HuR enhances p53 translation in response to ultraviolet light irradiation. Proc. Natl Acad. Sci. USA 100, 8354-8359

Duke University, Durham, North Carolina, United States
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 08/2003; 100(14):8354-9. DOI: 10.1073/pnas.1432104100
Source: PubMed


Exposure to short-wavelength UV light (UVC) strongly induces p53 expression. In human RKO colorectal carcinoma cells, this increase was not due to elevated p53 mRNA abundance, cytoplasmic export of p53 mRNA, or UVC-triggered stabilization of the p53 protein. Instead, p53 translation was potently enhanced after UVC irradiation. The 3' UTR of p53 was found to be a target of the RNA-binding protein HuR in a UVC-dependent manner in vitro and in vivo. HuR-overexpressing RKO cells displayed elevated p53 levels, whereas cells expressing reduced HuR showed markedly diminished p53 abundance and p53 translation. Our results demonstrate a role for HuR in binding to the p53 mRNA and enhancing its translation.

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    • "Earlier observations had shown that the caspase-dependent cleavage of HuR contributes to apoptotic progression in cells exposed to lethal stresses[64]. Although the consequences of HuR cleavage on the expression of HuR-bound mRNAs have not been investigated in this study, one can speculate that known HuR mRNA ligands such as pro-apoptotic p53[65]and cell growth inhibitor p21[66]mRNAs might be stabilized and thereby contribute to the observed apoptotic phenotype. "
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    ABSTRACT: Nearly twenty years after its identification as a new β-karyopherin mediating the nuclear import of the RNA-binding protein hnRNP A1, Transportin-1 is still commonly overlooked in comparison with its best known cousin, Importin-β. Transportin-1 is nonetheless a considerable player in nucleo-cytoplasmic transport. Over the past few years, significant progress has been made in the characterization of the nuclear localization signals (NLSs) that Transportin-1 recognizes, thereby providing the molecular basis of its diversified repertoire of cargoes. The recent discovery that mutations in the Transportin-dependent NLS of FUS cause mislocalization of this protein and result in amyotrophic lateral sclerosis illustrates the importance of Transportin-dependent import for human health. Besides, new functions of Transportin-1 are emerging in processes other than nuclear import. Here, we summarize what is known about Transportin-1 and the related β-karyopherin Transportin-2.
    Full-text · Article · Apr 2014 · FEBS letters
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    • "Previously, we showed that RNPC1, a RNA binding protein and p53 family target, can modulate p63 expression via mRNA stability, but regulates p53 expression via mRNA translation [19], [30]. In addition, HuR, another RNA binding protein, positively regulates p53 mRNA stability and translation, but is only found to regulates p63 mRNA translation [20], [31], [32]. In this study, we showed that PCBP1 can directly bind to p63 mRNA via CU-rich element in 3′UTR and the CUE is responsive to PCBP1. "
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    ABSTRACT: p63, a transcription factor and p53 family protein, plays a crucial role in tumor suppression and development of various epithelial tissues. While p63 expression is controlled mostly by post-translational modifications, recent studies indicate that transcriptional and posttranscriptional regulations are essential for proper p63 expression. Here, we investigated the regulation of p63 expression by poly (C)-binding protein 1 (PCBP1, also known as hnRNP-E1 and αCP1). We found that knockdown of PCBP1 decreases the level of p63 transcript and protein. We also found that PCBP1 regulates the stability of p63 mRNA via binding to p63 3'UTR. Additionally, we found that a CU-rich element (CUE) in p63 3'UTR is bound by and responsive to PCBP1. Together, we conclude that PCBP1 regulates p63 expression via mRNA stability.
    Full-text · Article · Aug 2013 · PLoS ONE
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    • "Translation regulation can also occur through the 3′-UTR. For instance, HuR was shown to bind to either the AU-rich or the U-rich regions of the p53 3′-UTR, leading to an increase in p53 translation after UVC treatment43. On the other hand, RNPC1 functions as a translational repressor by binding to the 5′- and 3′-UTR of p53 mRNA so that it prevents cap-binding protein eIF4E from binding to p53 mRNA30. "
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    ABSTRACT: It is well known that upon stress, the level of the tumor suppressor p53 is remarkably elevated. However, despite extensive studies, the underlying mechanism involving important inter-players for stress-induced p53 regulation is still not fully understood. We present evidence that the human lincRNA-RoR (RoR) is a strong negative regulator of p53. Unlike MDM2 that causes p53 degradation through the ubiquitin-proteasome pathway, RoR suppresses p53 translation through direct interaction with the heterogeneous nuclear ribonucleoprotein I (hnRNP I). Importantly, a 28-base RoR sequence carrying hnRNP I binding motifs is essential and sufficient for p53 repression. We further show that RoR inhibits p53-mediated cell cycle arrest and apoptosis. Finally, we demonstrate a RoR-p53 autoregulatory feedback loop where p53 transcriptionally induces RoR expression. Together, these results suggest that the RoR-hnRNP I-p53 axis may constitute an additional surveillance network for the cell to better respond to various stresses.Cell Research advance online publication 4 December 2012; doi:10.1038/cr.2012.164.
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