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
RNA-binding protein RNPC1 acts as an oncogene in gastric cancer by stabilizing aurora kinase B mRNA.
TL;DR: In this article, the role of RNPC1 in gastric cancer and the underlying mechanisms are still unclear, however, it is reported to act as a tumor suppressor by binding and regulating the expression of target genes in various cancers.
Journal ArticleDOI
RBM38 Reverses Sorafenib Resistance in Hepatocellular Carcinoma Cells by Combining and Promoting lncRNA-GAS5
Xing Gao,Cheng Lu,Ziyu Liu,Yan Lin,Julu Huang,Lu Lu,Xi Huang,Ziqin He,Xiaomin She,Rong Liang,Jiazhou Ye +10 more
TL;DR: In this paper , the role of the tumor suppressor RBM38 and its potential to reverse sorafenib resistance was examined, and the molecular mechanisms underlying the binding of RBM 38 and the lncRNA GAS5 were examined.
Journal ArticleDOI
RNA binding protein and microRNA control of endothelial cell function
Journal ArticleDOI
Cumulative effects of weakly repressive regulatory regions in the 3’ UTR maintain PD-1 expression homeostasis in mammals
Panpan Wang,Wenxue Zhao +1 more
TL;DR: In this article , the PD-1 3' UTR was found to be functionally conserved and strongly repressed gene expression through many common RBP binding sites, which might represent a general model for how small regulatory effects play big roles in regulation of gene expression and biology.
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.