Document Detail

Polyubiquitinated Tristetraprolin protects from TNF-induced, Caspase-mediated Apoptosis.
MedLine Citation:
PMID:  25056949     Owner:  NLM     Status:  Publisher    
Binding of tumor necrosis factor (TNF) to its receptor (TNFR1) elicits the spatiotemporal assembly of two signaling complexes that coordinate the balance between cell survival and cell death. We have shown previously that following TNF treatment, the mRNA-decay protein Tristetraprolin (TTP) is K63-polyubiquitinated by TNF-receptor associated factor 2 (TRAF2), suggesting a regulatory role in TNFR signaling. Here, we demonstrate that TTP interacts with the TNFR1 in a TRAF2 dependent manner, thereby initiating the MEKK1/MKK4-dependent activation of c-Jun-N-terminal kinase (JNK) activities. This regulatory function towards JNK, but not NF-κB activation depends on TTPs lysine 105, which we identified as the corresponding TRAF2 ubiquitination site. Disabling TTP polyubiquitination results in enhanced TNF-induced apoptosis in cervical cancer cells. Together, we uncover a novel aspect of TNFR1 signaling, where TTP, in alliance with TRAF2, acts as balancer of JNK mediated cell survival versus death.
Ulrike Resch; Angelica Cuapio; Caterina Sturtzel; Erhard Hofer; Rainer de Martin; Yvonne M Holper-Schichl
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-7-23
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  -     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2014 Jul 
Date Detail:
Created Date:  2014-7-24     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2014, The American Society for Biochemistry and Molecular Biology.
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