p73 expression is regulated by RNPC1, a target of the p53 family, via mRNA stability.
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TLDR
The mutual regulation between p73 and RNPC1 constitutes a novel feed-forward loop, which might be explored as a target for tumors without a functional p53.Abstract:
p73, a p53 family tumor suppressor, is expressed as TA and ΔN isoforms. Due to the role of p73 in tumor suppression and neural development, its expression and activity are tightly regulated by multiple mechanisms, including transcription and posttranslational modifications. Here, we found that p73 mRNA stability is regulated by RNPC1, an RNA binding protein and a target of the p53 family. We also showed that a CU-rich element in the 3′ untranslated region of p73 is recognized by and responsive to RNPC1. To explore the physiological significance of RNPC1-regulated p73 expression, we showed that the loss of RNPC1 in p53-null mouse embryonic fibroblasts leads to reduced expression of p73, along with decreased expression of p21, p130, and γ-H2A.X, and consequently a decreased number of senescent cells. Furthermore, we observed that knockdown of TAp73 or p21, another target of RNPC1, attenuates the inhibitory effect of RNPC1 on cell proliferation and premature senescence, whereas combined knockdown of TAp73 and p21 completely abolishes it. Due to the fact that RNPC1 is a target of p73, the mutual regulation between p73 and RNPC1 constitutes a novel feed-forward loop, which might be explored as a target for tumors without a functional p53.read more
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Mice deficient in Rbm38, a target of the p53 family, are susceptible to accelerated aging and spontaneous tumors.
Jin Zhang,Enshun Xu,Cong Ren,Wensheng Yan,Min Zhang,Mingyi Chen,Robert D. Cardiff,Denise M. Imai,Erik R. Wisner,Xinbin Chen +9 more
TL;DR: The results suggest that Rbm38 is necessary for normal hematopoiesis and for suppressing accelerated aging and tumorigenesis and the p53-Rbm38 axis might be explored for extending longevity and for tumor suppression.
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A balancing act: orchestrating amino-truncated and full-length p73 variants as decisive factors in cancer progression
TL;DR: The novel properties of DNp73 in the invasion metastasis cascade are described and the comprehensive p73 regulatome is outlined with an emphasis on molecular processes putting TAp73 out of action in advanced tumors to provoke a new understanding of the acquisition of aggressive traits by cancer cells.
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MDM2 expression is repressed by the RNA-binding protein RNPC1 via mRNA stability.
Enshun Xu,Jin Zhang,Xinbin Chen +2 more
TL;DR: The RNA-binding protein (RBP) RNPC1 is a target of the p53 family and forms a feedback regulatory loop with the p 53 family proteins and is able to destabilize the MDM2 transcript via binding to multiple AU-/U-rich elements inMDM2 3′untranslated region (3′UTR).
References
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Tiina Peritz,Fanyi Zeng,Fanyi Zeng,Theresa J Kannanayakal,Kalle Kilk,Emelía Eiríksdóttir,Ülo Langel,James Eberwine +7 more
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Isoform-specific p73 knockout mice reveal a novel role for ΔNp73 in the DNA damage response pathway
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Journal ArticleDOI
Expression of ΔNp73 is a molecular marker for adverse outcome in neuroblastoma patients
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TL;DR: The data seem to indicate that ΔNp73 is a crucial gene in neuroblastoma pathogenesis, and its role in predicting a poorer outcome is independent from age, primary tumor site, stage and MYCN amplification.
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Transactivation-deficient ΔTA-p73 Inhibits p53 by Direct Competition for DNA Binding IMPLICATIONS FOR TUMORIGENESIS
TL;DR: It is shown that up-regulation of endogenous p73 just like ectopic overexpression of DeltaTA-p73 confers resistance to p53-mediated apoptosis induced by the chemotherapeutic agent H-7, and this data strongly support a role ofDeltaTA- p73 expression for tumor formation.
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GPX2, a Direct Target of p63, Inhibits Oxidative Stress-induced Apoptosis in a p53-dependent Manner
Wensheng Yan,Xinbin Chen +1 more
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