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.

ZFP36 stabilizes RIP1 via degradation of XIAP and cIAP2 thereby promoting ripoptosome assembly / Selmi, Tommaso; Alecci, Claudia; Dell' Aquila, Miriam; Montorsi, Lucia; Martello, Andrea; Guizzetti, Filippo; Volpi, Nicola; Parenti, Sandra; Ferrari, Sergio; Salomoni, Paolo; Grande, Alexis; ZANOCCO MARANI, Tommaso. - In: BMC CANCER. - ISSN 1471-2407. - ELETTRONICO. - 15:1(2015), pp. 1-7. [10.1186/s12885-015-1388-5]

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

SELMI, TOMMASO;ALECCI, CLAUDIA;MONTORSI, LUCIA;MARTELLO, Andrea;VOLPI, Nicola;PARENTI, Sandra;FERRARI, Sergio;GRANDE, Alexis;ZANOCCO MARANI, Tommaso
2015

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.
2015
15
1
1
7
ZFP36 stabilizes RIP1 via degradation of XIAP and cIAP2 thereby promoting ripoptosome assembly / Selmi, Tommaso; Alecci, Claudia; Dell' Aquila, Miriam; Montorsi, Lucia; Martello, Andrea; Guizzetti, Filippo; Volpi, Nicola; Parenti, Sandra; Ferrari, Sergio; Salomoni, Paolo; Grande, Alexis; ZANOCCO MARANI, Tommaso. - In: BMC CANCER. - ISSN 1471-2407. - ELETTRONICO. - 15:1(2015), pp. 1-7. [10.1186/s12885-015-1388-5]
Selmi, Tommaso; Alecci, Claudia; Dell' Aquila, Miriam; Montorsi, Lucia; Martello, Andrea; Guizzetti, Filippo; Volpi, Nicola; Parenti, Sandra; Ferrari,...espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/1074886
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