p73 expression is regulated by RNPC1, a target of the p53 family, via mRNA stability.
Reads0
Chats0
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
Citations
More filters
Journal ArticleDOI
Disruption of the Rbm38-eIF4E Complex with a Synthetic Peptide Pep8 Increases p53 Expression.
TL;DR: Disruption of the Rbm38-eIF4E complex via synthetic peptides induces wild-type p53 expression, suppresses tumor growth and progression, and may serve as a novel cancer therapeutic strategy.
Journal ArticleDOI
RNPC1, an RNA-binding Protein and a p53 Target, Regulates Macrophage Inhibitory Cytokine-1 (MIC-1) Expression through mRNA Stability
TL;DR: A novel post-transcriptional mechanism is found to regulate MIC-1 expression by RNPC1 via mRNA stability, and it is shown that overexpression of RNA-binding proteinRNPC1 can increase, whereas knockdown or knock-out of RN PC1 decreases, MIC- 1 transcript and protein levels.
Journal ArticleDOI
The RNA binding proteins RBM38 and DND1 are repressed in AML and have a novel function in APL differentiation.
TL;DR: Results indicate that expression of the RNA binding proteins RBM38 and DND1 is repressed in primary AML patients, that neutrophil differentiation is dependent on increased expression of both proteins, and that these proteins have a critical role in regulating p21(CIP1) expression during APL differentiation.
Journal ArticleDOI
PPM1D phosphatase, a target of p53 and RBM38 RNA-binding protein, inhibits p53 mRNA translation via dephosphorylation of RBM38
TL;DR: Findings provide evidence that the crosstalk between PPM1D and RBM38, both of which are targets and modulators of p53, has a critical role in p53 expression and activity.
Journal ArticleDOI
The expression of RNA-binding protein RBM38 decreased in renal cell carcinoma and represses renal cancer cell proliferation, migration, and invasion.
TL;DR: It is found that the expression of RBM38 was lower in renal cell carcinoma tissues and cell lines, and Kaplan–Meier analysis suggested that R BM38 acts as a tumor suppressor in renalcell carcinoma, which has the potential value for the prediction of renal cell cancer prognosis.
References
More filters
Journal ArticleDOI
Monoallelically expressed gene related to p53 at 1p36, a region frequently deleted in neuroblastoma and other human cancers.
Mourad Kaghad,Helene Bonnet,Annie Yang,Laurent Creancier,Jean-Christophe Biscan,A. Valent,Adrian Minty,Pascale Chalon,Jean-Michel Lelias,Xavier Dumont,Pascual Ferrara,Frank McKeon,Daniel Caput +12 more
TL;DR: The demonstration that p73 is monoallelically expressed supports the notion that it is a candidate gene in neuroblastoma and proposes that the disregulation of p73 contributes to tumorigenesis and that p53-related proteins operate in a network of developmental and cell cycle controls.
Journal ArticleDOI
p73-deficient mice have neurological, pheromonal and inflammatory defects but lack spontaneous tumours
Annie Yang,Nancy Walker,Roderick T. Bronson,Mourad Kaghad,Mariëtte A. Oosterwegel,Jacques Bonnin,Christine Vagner,Helene Bonnet,Pieter Dikkes,Arlene H. Sharpe,Frank McKeon,Daniel Caput +11 more
TL;DR: It is shown that mice functionally deficient for all p73 isoforms exhibit profound defects, including hippocampal dysgenesis, hydrocephalus, chronic infections and inflammation, as well as abnormalities in pheromone sensory pathways, and there is a marked divergence in the physiological functions of the p53 family members.
Journal ArticleDOI
The tyrosine kinase c-Abl regulates p73 in apoptotic response to cisplatin-induced DNA damage
JianGen Gong,Antonio Costanzo,Hong-Qiong Yang,Gerry Melino,William G. Kaelin,Massimo Levrero,Jean Y. J. Wang +6 more
TL;DR: The results indicate that c-Abl and p73 are components of a mismatch-repair-dependent apoptosis pathway which contributes to cisplatin-induced cytotoxicity.
Journal ArticleDOI
Role for the p53 homologue p73 in E2F-1-induced apoptosis
Meredith S. Irwin,Maria C. Marin,Andrew C. Phillips,Ratnam S. Seelan,David I. Smith,Wanguo Liu,Elsa R. Flores,Kenneth Y. Tsai,Tyler Jacks,Tyler Jacks,Karen H. Vousden,William G. Kaelin,William G. Kaelin +12 more
TL;DR: It is concluded that activation of p73 provides a means for E2F-1 to induce death in the absence of p53, and the transcription of the p53 homologue p73 is induced.
Journal ArticleDOI
RNA-binding proteins in human genetic disease.
TL;DR: It is concluded that defects in RNA metabolism caused by aberrations in RBPs might underlie a broader spectrum of complex human disorders.