Title |
ZFP36 stabilizes RIP1 via degradation of XIAP and cIAP2 thereby promoting ripoptosome assembly
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Published in |
BMC Cancer, May 2015
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DOI | 10.1186/s12885-015-1388-5 |
Pubmed ID | |
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 |
Abstract |
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. 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. 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. 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. |
X Demographics
Geographical breakdown
Country | Count | As % |
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Unknown | 3 | 100% |
Demographic breakdown
Type | Count | As % |
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Practitioners (doctors, other healthcare professionals) | 1 | 33% |
Members of the public | 1 | 33% |
Scientists | 1 | 33% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 18 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 6 | 33% |
Student > Doctoral Student | 2 | 11% |
Student > Bachelor | 2 | 11% |
Student > Master | 2 | 11% |
Researcher | 2 | 11% |
Other | 1 | 6% |
Unknown | 3 | 17% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 5 | 28% |
Immunology and Microbiology | 5 | 28% |
Agricultural and Biological Sciences | 4 | 22% |
Neuroscience | 1 | 6% |
Unknown | 3 | 17% |