Journal
BMC CANCER
Volume 15, Issue -, Pages -Publisher
BMC
DOI: 10.1186/s12885-015-1388-5
Keywords
ZFP36; Ripoptosome; XIAP; cIAP2; RIP1; Glioma; Necroptosis
Categories
Funding
- AIL fellowship (Associazione Italiana contro le leucemielinfomi e mieloma)
- The Brain Tumour Charity [8/197] Funding Source: researchfish
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available