9 research outputs found
BCL9L expression in pancreatic neoplasia with a focus on SPN: a possible explanation for the enigma of the benign neoplasia
Additional file 1: of BCL9L expression in pancreatic neoplasia with a focus on SPN: a possible explanation for the enigma of the benign neoplasia
Mean RNA expression Ratio derived from two independent experiments, normalized against GAPDH. (XLSX 12 kb
Incidence of EGFR, kras, BRAF, ALK, and p53 alterations in a cohort of 218 consecutively tested patients from a certified lung cancer center: Correlation with clinical characteristics and treatment outcome.
Intercalated EGFR TKI and chemotherapy induction therapy in EGFR mt+ NSCLC stage IIIA and IIIB: report of 5 cases.
Inhibition of TNF receptor 1 internalization by adenovirus 14.7K as a novel immune escape mechanism
The adenoviral protein E3-14.7K (14.7K) is an inhibitor of TNF-induced apoptosis, but the molecular mechanism underlying this protective effect has not yet been explained exhaustively. TNF-mediated apoptosis is initiated by ligand-induced recruitment of TNF receptor–associated death domain (TRADD), Fas-associated death domain (FADD), and caspase-8 to the death domain of TNF receptor 1 (TNFR1), thereby establishing the death-inducing signaling complex (DISC). Here we report that adenovirus 14.7K protein inhibits ligand-induced TNFR1 internalization. Analysis of purified magnetically labeled TNFR1 complexes from murine and human cells stably transduced with 14.7K revealed that prevention of TNFR1 internalization resulted in inhibition of DISC formation. In contrast, 14.7K did not affect TNF-induced NF-κB activation via recruitment of receptor-interacting protein 1 (RIP-1) and TNF receptor–associated factor 2 (TRAF-2). Inhibition of endocytosis by 14.7K was effected by failure of coordinated temporal and spatial assembly of essential components of the endocytic machinery such as Rab5 and dynamin 2 at the site of the activated TNFR1. Furthermore, we found that the same TNF defense mechanisms were instrumental in protecting wild-type adenovirus–infected human cells expressing 14.7K. This study describes a new molecular mechanism implemented by a virus to escape immunosurveillance by selectively targeting TNFR1 endocytosis to prevent TNF-induced DISC formation