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The novel p53 target gene IRF2BP2 participates in cell survival during the p53 stress response

Max Koeppel, Simon J. van Heeringen, Leonie Smeenk, Anna C. Navis, Eva M. Janssen-Megens, Marion Lohrum
2008 Nucleic Acids Research  
Here, we describe the interferon regulatory factor-2-binding protein-2 (IRF2BP2) as a new direct target gene of p53, influencing the p53-mediated cellular decision.  ...  Analyzing the molecular functions of IRF2BP2, it appears to be able to impede on the p53-mediated transactivation of the p21-and the Bax-gene.  ...  ACKNOWLEDGEMENTS We thank Stephen Goodbourn for IRF2BP2-constructs, Yugang Tu and Moshe Oren for the p53-responsive luciferase constructs and Karen Vousden for providing us with p53-expression plasmids  ... 
doi:10.1093/nar/gkn940 pmid:19042971 pmcid:PMC2632907 fatcat:tfso27afcbg5nidsdxpujk3wb4

Mutant p53 Protects Cells from 12-O-Tetradecanoylphorbol-13-Acetate-Induced Death by Attenuating Activating Transcription Factor 3 Induction

Y. Buganim, E. Kalo, R. Brosh, H. Besserglick, I. Nachmany, Y. Rais, P. Stambolsky, X. Tang, M. Milyavsky, I. Shats, M. Kalis, N. Goldfinger (+1 others)
2006 Cancer Research  
Mutagenesis analysis of the ATF3 promoter identified the regulatory motifs cyclic AMP-responsive element binding protein/ATF and MEF2 as being responsible for the TPA-induced activation of ATF3.  ...  Mutations in p53 are ubiquitous in human tumors. Some p53 mutations not only result in loss of wild-type (WT) activity but also grant additional functions, termed "gain of function."  ...  Using the MatInspector database (39), we found that this promoter region harbors three known regu-latory motifs [i.e., MEF2, CREB/ATF, and CAAT/enhancer binding protein (C/EBP)].  ... 
doi:10.1158/0008-5472.can-06-0916 pmid:17108111 fatcat:ryafxxo7abbv5id3neofj37qty

Naturally occurring germline and tumor-associated mutations within the ATP-binding motifs of PTEN lead to oxidative damage of DNA associated with decreased nuclear p53

Xin He, Ying Ni, Yu Wang, Todd Romigh, Charis Eng
2010 Human Molecular Genetics  
Recent identification of naturally occurring cancer and germline mutations within the ATP-binding motifs of PTEN (heretofore referred to as PTEN ATP-binding mutations) has revealed that these mutations  ...  disrupted the subcellular localization and tumor-suppressor activity of PTEN.  ...  Because tumor protein 53-induced nuclear protein 1 (TP53INP1) is a major mediator of p53 antioxidant function, we further compared TP53INP1 mRNA levels in MCF-7 cell lines expressing the FLAG-tagged PTEN  ... 
doi:10.1093/hmg/ddq434 pmid:20926450 pmcid:PMC3000677 fatcat:mkm6k6l5ejevpesfd35dqo5giy

Characterization of genome-wide p53-binding sites upon stress response

Leonie Smeenk, Simon J. van Heeringen, Max Koeppel, Marc A. van Driel, Stefanie J. J. Bartels, Robert C. Akkers, Sergei Denissov, Hendrik G. Stunnenberg, Marion Lohrum
2008 Nucleic Acids Research  
Using this collection of genome-wide binding sites, a new high-confidence algorithm was developed, p53scan, to identify the p53 consensus-binding motif.  ...  To understand p53's essential transcriptional functions, unbiased analysis of its DNA-binding repertoire is pivotal.  ...  Vousden for p53-constructs; Dr H. van Bokhoven for p63-constructs and Drs Shinji Takagi and G. Melino for p73-constructs.  ... 
doi:10.1093/nar/gkn232 pmid:18474530 pmcid:PMC2441782 fatcat:rsjtbreldvhrbcz3qfltgmegue

Functional Characterization of Nupr1L, A Novel p53-Regulated Isoform of the High-Mobility Group (HMG)-Related Protumoral Protein Nupr1

Maria Belen Lopez, Maria Noé Garcia, Daniel Grasso, Jennifer Bintz, Maria Inés Molejon, Gabriel Velez, Gwen Lomberk, Jose Luis Neira, Raul Urrutia, Juan Iovanna
2015 Journal of Cellular Physiology  
Experiments using reporter assays combined with site-directed mutagenesis and using cells with controllable p53 expression demonstrate that both of these sequences are responsible for the regulation of  ...  We have previously demonstrated a crucial role of NUPR1 in tumor development and progression.  ...  Acknowledgements This work was supported by La Ligue Contre le Cancer, INCa, Canceropole PACA, DGOS (labelization SIRIC) and INSERM (to JLI), National Institutes of Health Grants DK52913, the Mayo Clinic  ... 
doi:10.1002/jcp.25022 pmid:25899918 pmcid:PMC4778741 fatcat:jwksmcpjnbdrzdbfxhzgkxsxx4

EGR-1 forms a complex with YAP-1 and upregulates Bax expression in irradiated prostate carcinoma cells

M Zagurovskaya, M M Shareef, A Das, A Reeves, S Gupta, M Sudol, M T Bedford, J Prichard, M Mohiuddin, M M Ahmed
2009 Oncogene  
Dominant-negative EGR-1 mutant (dnEGR-1) or repressor of EGR-1, NGFIA binding protein 1 (NAB1), increased radioresistance of these cells.  ...  In this study, we investigated the functional role of early growth response-1 (Egr1 gene) in the regulation of radiation-induced clonogenic inhibition and apoptosis in p53 wild-type and mutant prostate  ...  DK62345) and Pennsylvania Department of Health Grant (SAP4100037378) to MMS and Welch Foundation Grant (G-1495) to MTB.  ... 
doi:10.1038/onc.2008.461 pmid:19137013 fatcat:3s4r4q5ihfenfgoblzunqqmxmu

p53-repressed miRNAs are involved with E2F in a feed-forward loop promoting proliferation

Ran Brosh, Reut Shalgi, Atar Liran, Gilad Landan, Katya Korotayev, Giang Huong Nguyen, Espen Enerly, Hilde Johnsen, Yosef Buganim, Hilla Solomon, Ido Goldstein, Shalom Madar (+7 others)
2008 Molecular Systems Biology  
Indicative of their significance, expression of these miRNAs is downregulated in senescent cells and in breast cancers harboring wild-type p53.  ...  Here we investigated the mammalian cell proliferation control network consisting of transcriptional regulators, E2F and p53, their targets and a family of 15 miRNAs.  ...  Providing further support, the promoters of the mRNAs from the 'cell-cycle-associated co-cluster' are highly enriched with E2F-binding motifs ( Figure 3F ), and in particular, a conserved E2F-binding  ... 
doi:10.1038/msb.2008.65 pmid:19034270 pmcid:PMC2600669 fatcat:khhyqv5cebe6platqirkohmdt4

The N-terminal Interferon-binding Domain (IBiD) Homology Domain of p300 Binds to Peptides with Homology to the p53 Transactivation Domain

Lee Finlan, Ted R. Hupp
2004 Journal of Biological Chemistry  
This minimal IHD miniprotein can function in vivo as a p53-binding polypeptide in assays including: (i) complex formation with VP16-LXXLL peptide motifs in the two-hybrid assay; (ii) action as a dominant  ...  negative inhibitor of p53 from p21 luciferase templates; and (iii) attenuation of endogenous p21 protein levels.  ...  of p53 and loss of proliferative control (19) , thereby supporting the notion that T-antigen has another mechanism of disrupting the critical activities of tumor suppressor proteins.  ... 
doi:10.1074/jbc.m405974200 pmid:15337767 fatcat:3eohgxs4izcctn5tsypotmu4qm

A Genomic Map of p53 Binding Sites Identifies Novel p53 Targets Involved in an Apoptotic Network

Chaouki Miled, Marco Pontoglio, Serge Garbay, Moshe Yaniv, Jonathan B. Weitzman
2005 Cancer Research  
The transcriptional activity of the p53 protein is central to its role in tumor suppression.  ...  Using a computational approach, we generated a genome-wide map of p53 binding sites (p53BS) to identify novel p53 target genes.  ...  Acknowledgments The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C.  ... 
doi:10.1158/0008-5472.can-04-4232 pmid:15958553 fatcat:gxuhcvjsanbrrkjksbbfnj4iei

Phosphorylation-Dependent PIH1D1 Interactions Define Substrate Specificity of the R2TP Cochaperone Complex

Zuzana Hořejší, Lasse Stach, Thomas G. Flower, Dhira Joshi, Helen Flynn, J. Mark Skehel, Nicola J. O'Reilly, Roksana W. Ogrodowicz, Stephen J. Smerdon, Simon J. Boulton
2014 Cell Reports  
motif within TEL2, are essential and sufficient for binding.  ...  Here, we describe a phosphopeptide binding domain (PIH-N) in the PIH1D1 subunit of the R2TP complex that preferentially binds to highly acidic phosphorylated proteins.  ...  S.J.S is grateful to the MRC for its continuing support (U117584228) and to Philip Walker and the staff at Diamond Light Source (UK) for assistance with X-ray data collection.  ... 
doi:10.1016/j.celrep.2014.03.013 pmid:24656813 pmcid:PMC3989777 fatcat:p4qulxmqhvblld5mlakwrnptky

Regulation of the MicroRNA Processor DGCR8 by the Tumor Suppressor ING1

D. Gomez-Cabello, S. Callejas, A. Benguria, A. Moreno, J. Alonso, I. Palmero
2010 Cancer Research  
ING proteins are functionally linked to the p53 pathway, and they participate in transcriptional control via the recognition of histone marks and recruitment of protein complexes with chromatin-modifying  ...  The ING family of tumor suppressor proteins controls several cellular functions relevant to antitumor protection, such as cell cycle control, apoptosis, senescence, or migration.  ...  Grant Support  ... 
doi:10.1158/0008-5472.can-09-2088 pmid:20179197 fatcat:vmblztjakbf3rohlckiu7pbi7m

Crosstalk between c-Jun and TAp73α/β contributes to the apoptosis–survival balance

Max Koeppel, Simon J. van Heeringen, Daniela Kramer, Leonie Smeenk, Eva Janssen-Megens, Marianne Hartmann, Hendrik G. Stunnenberg, Marion Lohrum
2011 Nucleic Acids Research  
We identified a specific p73 consensus binding motif and found a strong enrichment of AP1 motifs in close proximity to binding sites for TAp73a.  ...  The p53-family member p73 plays a role in various cellular signaling pathways during development and growth control and it can have tumor suppressor properties.  ...  Besides its function as a pro-apoptotic protein, several reports have also described an inhibition of apoptosis or a support of growth by TAp73 in certain cell lines under specific conditions (19, 20)  ... 
doi:10.1093/nar/gkr028 pmid:21459846 pmcid:PMC3152320 fatcat:gtgoveyo5ff6pesvzzjryz3lga

Ionizing Radiation-inducible Apoptosis in the Absence of p53 Linked to Transcription Factor EGR-1

Mansoor M. Ahmed, Stephen F. Sells, Kolaparthi Venkatasubbarao, Sana M. Fruitwala, Sumathi Muthukkumar, Cindy Harp, Mohammed Mohiuddin, Vivek M. Rangnekar
1997 Journal of Biological Chemistry  
The tumor suppressor protein p53 is a pivotal regulator of apoptosis, and prostate cancer cells that lack p53 protein are moderately resistant to apoptotic death by ionizing radiation.  ...  Induction of the TNF-␣ gene by ionizing radiation and EGR-1 was mediated via a GC-rich EGR-1-binding motif in the TNF-␣ promoter.  ...  Because p53 protein is mutated and non-functional in a large number of prostate tumors (14, 15) , it is imperative to identify other proapoptotic genes that can function via a p53-independent mechanism  ... 
doi:10.1074/jbc.272.52.33056 pmid:9407088 fatcat:ckaamesacnemrfufgywg7io6mu

MSK1 functions as a transcriptional coactivator of p53 in the regulation of p21 gene expression

Jihye Ahn, Jin Gyeong Lee, Chuevin Chin, Suna In, Aerin Yang, Hee-Sung Park, Jaehoon Kim, Jeong Hyeon Park
2018 Experimental and Molecular Medicine  
Here, using in vitro and cell-based transcription assays, we show that MSK1 functions as a transcriptional coactivator of p53 in p21 expression, an action associated with MAPK-dependent phosphorylation  ...  The kinase activity of MSK1 is activated by intramolecular autophosphorylation, which is initially triggered by the activation of upstream mitogen-activated protein kinases (MAPKs), such as p38 and ERK1  ...  Our findings support a novel connection between MSK1 and p53, showing that p53 has a direct role in the recruitment of MSK1 to p53-binding sites in the p21 locus, and further warrant a future genome-wide  ... 
doi:10.1038/s12276-018-0160-8 pmid:30305627 pmcid:PMC6180136 fatcat:xd5mct34czdannb6z25qcs452e

DNA-dependent Acetylation of p53 by the Transcription Coactivator p300

David Dornan, Harumi Shimizu, Neil D. Perkins, Ted R. Hupp
2002 Journal of Biological Chemistry  
The IHD or IBiD minidomains can bind to the p53 activation domain in vivo as determined using the mammalian two-hybrid VP16-GAL4 luciferase reporter assay.  ...  Co-transfection into cells of the p53 gene and plasmid DNA containing the consensus DNA binding site of p53 activated DNAdependent acetylation of p53 in vivo.  ...  Deborah French (University of Strathclyde, UK) for critical reading of the manuscript and helpful discussions.  ... 
doi:10.1074/jbc.m211460200 pmid:12499368 fatcat:3vel4zbwurcs7d2obqq33fmn3y
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