A novel p53 rescue compound induces p53-dependent growth arrest and sensitises glioma cells to Apo2L/TRAIL-induced apoptosis

Cell Death and Differentiation
L WeinmannM Weller

Abstract

Reactivation of mutant p53 in tumours is a promising strategy for cancer therapy. Here we characterise the novel p53 rescue compound P53R3 that restores sequence-specific DNA binding of the endogenously expressed p53(R175H) and p53(R273H) mutants in gel-shift assays. Overexpression of the paradigmatic p53 mutants p53(R175H), p53(R248W) and p53(R273H) in the p53 null glioma cell line LN-308 reveals that P53R3 induces p53-dependent antiproliferative effects with much higher specificity and over a wider range of concentrations than the previously described p53 rescue drug p53 reactivation and induction of massive apoptosis (PRIMA-1). Furthermore, P53R3 enhances recruitment of endogenous p53 to several target promoters in glioma cells bearing mutant (T98G) and wild-type (LNT-229) p53 and induces mRNA expression of numerous p53 target genes in a p53-dependent manner. Interestingly, P53R3 strongly enhances the mRNA, total protein and cell surface expression of the death receptor death receptor 5 (DR5) whereas CD95 and TNF receptor 1 levels are unaffected. Accordingly, P53R3 does not sensitise for CD95 ligand- or tumour necrosis factor alpha-induced cell death, but displays synergy with Apo2L.0 in 9 of 12 glioma cell lines. Both DR5 s...Continue Reading

References

Jan 1, 1981·Advances in Cancer Research·M C Berenbaum
Aug 1, 1995·European Journal of Immunology·A Rensing-EhlA Fontana
May 15, 1997·Nature·Y HauptM Oren
Nov 5, 1997·Nature Genetics·G S WuW S el-Deiry
Jun 24, 1998·Cell and Tissue Research·M Weller
Jun 5, 1998·FEBS Letters·J RiegerM Weller
Jan 5, 2000·Science·B A FosterF Rastinejad
Feb 11, 2000·Radiation Research·R K Schmidt-UllrichK Valerie
Feb 13, 2001·European Journal of Pharmacology·F SchmidtM Weller
May 31, 2001·Journal of Cellular Physiology·B GuanS Y Sun
Mar 5, 2002·Nature Medicine·Vladimir J N BykovGalina Selivanova
Mar 23, 2002·Science·Thijn R BrummelkampReuven Agami
Apr 12, 2002·Oncogene·Thomas M RippinAlan R Fersht
Jan 16, 2003·Cell·Anatoly Y NikolaevWei Gu
Dec 3, 2003·Proceedings of the National Academy of Sciences of the United States of America·Shulin Wang, Wafik S El-Deiry
Jul 10, 2004·Cell Death and Differentiation·J WischhusenM Weller
Aug 17, 2004·The Journal of Biological Chemistry·Mark J DemmaBimalendu Dasmahapatra
Dec 22, 2006·Cell·Carla P MartinsGerard I Evan
Jan 26, 2007·Nature·Andrea VenturaTyler Jacks

❮ Previous
Next ❯

Citations

Sep 25, 2009·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Yosef Buganim, Varda Rotter
Jul 24, 2012·Carcinogenesis·Dawid WalerychGiannino Del Sal
Feb 1, 2012·The Cancer Journal·Michael WellerWolfgang Wick
May 20, 2014·Molecular Diagnosis & Therapy·Anubhav JainPrakash S Bisen
Jan 14, 2012·Expert Opinion on Therapeutic Targets·Alexander H Stegh
Apr 15, 2014·FEBS Letters·Galina Selivanova
Apr 29, 2014·FEBS Letters·Vladimir J N Bykov, Klas G Wiman
Feb 19, 2010·Translational Oncology·Zhen Wang, Yi Sun
Jan 7, 2016·Frontiers in Oncology·Alejandro Parrales, Tomoo Iwakuma
May 28, 2011·European Journal of Cell Biology·Steffen KrausDorit K Nägler
Jan 29, 2011·Cancer Letters·Günter Eisele, Michael Weller
Mar 9, 2010·Seminars in Cancer Biology·Galina Selivanova
Jun 8, 2011·International Journal of Cancer. Journal International Du Cancer·Rosa Linda MessinaFrancesco Frasca
Mar 24, 2015·Biochimica Et Biophysica Acta·Evelyn N KouwenhovenHuiqing Zhou
Jan 1, 2013·Rare Diseases·Huiqing Zhou, Daniel Aberdam
Jan 26, 2011·Cancer Biology & Therapy·Hope M AmmDonald J Buchsbaum
Dec 1, 2014·Pathology, Research and Practice·Anne TellerSabine Franke
May 3, 2005·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Sarah L McDonaldAndrew C Schofield
Jul 14, 2007·Vitamins and Hormones·Howard P Glauert
Nov 30, 2016·International Journal of Molecular Sciences·David J Olivos, Lindsey D Mayo
Apr 2, 2013·Proceedings of the National Academy of Sciences of the United States of America·Ksenya ShchorsGerard I Evan
Mar 30, 2017·Pharmacology & Therapeutics·Daniel NguyenHua Lu
Sep 28, 2017·Nature Reviews. Clinical Oncology·Kanaga Sabapathy, David P Lane
Dec 7, 2018·Journal of Molecular Cell Biology·Xiang ZhouHua Lu
Jan 12, 2019·British Journal of Pharmacology·Yang LiKun Huang
Mar 3, 2019·International Journal of Molecular Sciences·Gabriele D MaurerJoachim P Steinbach
Dec 16, 2017·Nature Reviews. Cancer·Vladimir J N BykovKlas G Wiman
Nov 18, 2018·Current Medicinal Chemistry·Elizabeth A LopesMaria M M Santos
Apr 25, 2020·Biomolecules·Jerson L SilvaVitor F Ferreira
Jul 28, 2020·Protein Science : a Publication of the Protein Society·Dennis Bromley, Valerie Daggett
Jun 24, 2017·Cellular and Molecular Life Sciences : CMLS·Dekuang ZhaoPowel H Brown
Dec 24, 2018·Cancers·Satomi Yamamoto, Tomoo Iwakuma
Sep 12, 2018·Cancers·Ying ZhangRoger Abounader
Mar 16, 2018·Oncogene·Jonuelle AcostaDavid M Feldser
May 14, 2019·International Journal of Oncology·Iris Maria ForteAntonio Giordano
Dec 5, 2019·International Journal of Molecular Sciences·Hui LiKa Fai To

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis