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BMC Cancer
Published in: BMC Cancer 1/2015

Open Access 01-12-2015 | Research article

ZFP36 stabilizes RIP1 via degradation of XIAP and cIAP2 thereby promoting ripoptosome assembly

Authors: Tommaso Selmi, Claudia Alecci, Miriam dell’ Aquila, Lucia Montorsi, Andrea Martello, Filippo Guizzetti, Nicola Volpi, Sandra Parenti, Sergio Ferrari, Paolo Salomoni, Alexis Grande, Tommaso Zanocco-Marani

Published in: BMC Cancer | Issue 1/2015

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Abstract

Background

ZFP36 is an mRNA binding protein that exerts anti-tumor activity in glioblastoma by triggering cell death, associated to an increase in the stability of the kinase RIP1.

Methods

We used cell death assays, size exclusion chromatography, Co-Immunoprecipitation, shRNA lentivectors and glioma neural stem cells to determine the effects of ZFP36 on the assembly of a death complex containing RIP1 and on the induction of necroptosis.

Results

Here we demonstrate that ZFP36 promotes the assembly of the death complex called Ripoptosome and induces RIP1-dependent death. This involves the depletion of the ubiquitine ligases cIAP2 and XIAP and leads to the association of RIP1 to caspase-8 and FADD. Moreover, we show that ZFP36 controls RIP1 levels in glioma neural stem cell lines.

Conclusions

We provide a molecular mechanism for the tumor suppressor role of ZFP36, and the first evidence for Ripoptosome assembly following ZFP36 expression. These findings suggest that ZFP36 plays an important role in RIP1-dependent cell death in conditions where IAPs are depleted.
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Literature
1.
Sanduja S, Blanco FF, Young LE, Kaza V, Dixon DA. The role of tristetraprolin in cancer and inflammation. Front Biosci. 2012;17:174–88.CrossRef
2.
Stoecklin G, Gross B, Ming X-F, Moroni C. A novel mechanism of tumor suppression by destabilizing AU-rich growth factor mRNA. Oncogene. 2003;22:3554–61.CrossRefPubMed
3.
Al-Souhibani N, Al-Ahmadi W, Hesketh JE, Blackshear PJ, Khabar KSA. The RNA-binding zinc-finger protein tristetraprolin regulates AU-rich mRNAs involved in breast cancer-related processes. Oncogene. 2010;29:4205–15.CrossRefPubMedPubMedCentral
4.
Selmi T, Martello A, Vignudelli T, Ferrari E, Grande A, Gemelli C, et al. ZFP36 expression impairs glioblastoma cell lines viability and invasiveness by targeting multiple signal transduction pathways. Cell Cycle. 2012;11(10):977–87.CrossRef
5.
Rounbehler RJ, Fallahi M, Yang C, Steeves MA, Li W, Doherty JR, et al. Tristetraprolin impairs myc-induced lymphoma and abolishes the malignant state. Cell. 2012;150:563–74.CrossRefPubMedPubMedCentral
6.
Johnson BA, Blackwell TK. Multiple tristetraprolin sequence domains required to induce apoptosis and modulate responses to TNFalpha through distinct pathways. Oncogene. 2002;21:4237–46.CrossRefPubMed
7.
Kroemer G, Galluzzi L, Vandenabeele P, Abrams J, Alnemri ES, Baehrecke EH, et al. Classification of cell death: recommendations of the Nomenclature Committee on Cell Death 2009. Cell Death Differ. 2009;16:3–11.CrossRefPubMed
8.
Tenev T, Bianchi K, Darding M, Broemer M, Langlais C, Wallberg F, et al. The ripoptosome, a signaling platform that assembles in response to genotoxic stress and loss of IAPs. Mol Cell. 2011;43:432–48.CrossRefPubMed
9.
Feoktistova M, Geserick P, Kellert B, Dimitrova DP, Langlais C, Hupe M, et al. cIAPs Block Ripoptosome Formation, a RIP1/Caspase-8 Containing Intracellular Cell Death Complex Differentially Regulated by cFLIP Isoforms. Mol Cell. 2011;43:449–63.CrossRefPubMedPubMedCentral
10.
Thapa RJ, Basagoudanavar SH, Nogusa S, Irrinki K, Mallilankaraman K, Slifker MJ, et al. NF-kB protects cells from gamma interferon-induced RIP1-dependent necroptosis. Mol Cell Biol. 2011;31:2934–46.CrossRefPubMedPubMedCentral
11.
Thapa RJ, Nogusa S, Chen P, Maki JL, Lerro A, Andrake M, et al. Interferon-induced RIP1/RIP3-mediated necrosis requires PKR and is licensed by FADD and caspases. Proc Natl Acad Sci U S A. 2013;110:E3109–18.CrossRefPubMedPubMedCentral
12.
Kim CW, Kim HK, Vo M-T, Lee HH, Kim HJ, Min YJ, et al. Tristetraprolin controls the stability of cIAP2 mRNA through binding to the 3′UTR of cIAP2 mRNA. Biochem Biophys Res Commun. 2010;400(1):46–52.CrossRefPubMed
13.
Goffart N, Kroonen J, Rogister B. Glioblastoma-initiating cells: relationship with neural stem cells and the micro-environment. Cancers. 2013;5:1049–71.CrossRefPubMedPubMedCentral
14.
Bertrand MJM, Milutinovic S, Dickson KM, Ho WC, Boudreault A, Durkin J, et al. cIAP1 and cIAP2 facilitate cancer cell survival by functioning as E3 ligases that promote RIP1 ubiquitination. Mol Cell. 2008;30:689–700.CrossRefPubMed
15.
Wang H, Sun L, Su L, Rizo J, Liu L, Wang LF, et al. Mixed lineage kinase domain-like protein MLKL causes necrotic membrane disruption upon phosphorylation by RIP3. Mol Cell. 2014;54(1):133–46.CrossRefPubMed
16.
Zhang H, Zhou X, McQuade T, Li J, Chan FK-M, Zhang J. Functional complementation between FADD and RIP1 in embryos and lymphocytes. Nature. 2011;471:373–6.CrossRefPubMedPubMedCentral
17.
Lee E-W, Seo J-H, Jeong M-H, Lee S-S, Song J-W. The roles of FADD in extrinsic apoptosis and necroptosis. BMB Rep. 2012;45:496–508.CrossRefPubMed
18.
Pollard SM, Yoshikawa K, Clarke ID, Danovi D, Stricker S, Russell R, et al. Glioma stem cell lines expanded in adherent culture have tumor-specific phenotypes and are suitable for chemical and genetic screens. Cell Stem Cell. 2009;4:568–80.CrossRefPubMed
19.
Festjens N, Vanden Berghe T, Cornelis S, Vandenabeele P. RIP1, a kinase on the crossroads of a cell’s decision to live or die. Cell Death Differ. 2007;14:400–10.CrossRefPubMed
20.
Lee JY, Kim HJ, Yoon NA, Lee WH, Min YJ, Ko BK, et al. Tumor suppressor p53 plays a key role in induction of both tristetraprolin and let-7 in human cancer cells. Nucleic Acids Res. 2013;41(11):5614–25.CrossRefPubMedPubMedCentral
21.
Harkin DP, Bean JM, Miklos D, Song YH, Truong VB, Englert C, et al. Induction of GADD45 and JNK/SAPK-dependent apoptosis following inducible expression of BRCA1. Cell. 1999;97:575–86.CrossRefPubMed
22.
Sauer I, Schaljo B, Vogl C, Gattermeier I, Kolbe T, Müller M, et al. Interferons limit inflammatory responses by induction of tristetraprolin. Blood. 2006;107:4790–7.CrossRefPubMedPubMedCentral
23.
24.
Carballo E. Roles of tumor necrosis factor-alpha receptor subtypes in the pathogenesis of the tristetraprolin-deficiency syndrome. Blood. 2001;98:2389–95.CrossRefPubMed
25.
Schichl YM, Resch U, Lemberger CE, Stichlberger D, de Martin R, et al. Novel phosphorylation-dependent Ubiquitination of Tristetraprolin by MEK kinase 1 (MEKK1) and TNF-receptor associated factor 2 (TRAF2). J Biol Chem. 2011;286(44):38466–77.CrossRefPubMedPubMedCentral
Metadata
Title
ZFP36 stabilizes RIP1 via degradation of XIAP and cIAP2 thereby promoting ripoptosome assembly
Authors
Tommaso Selmi
Claudia Alecci
Miriam dell’ Aquila
Lucia Montorsi
Andrea Martello
Filippo Guizzetti
Nicola Volpi
Sandra Parenti
Sergio Ferrari
Paolo Salomoni
Alexis Grande
Tommaso Zanocco-Marani
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2015
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-015-1388-5

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