LitCoin-sentences  

PubMed:25622904 JSONTXT 27 Projects

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Id Subject Object Predicate Lexical cue
T1 0-112 Sentence denotes Inactivation of Sag/Rbx2/Roc2 e3 ubiquitin ligase triggers senescence and inhibits kras-induced immortalization.
T2 113-437 Sentence denotes Our recent study showed that SAG/RBX2 E3 ubiquitin ligase regulates apoptosis and vasculogenesis by promoting degradation of NOXA and NF1, and co-operates with Kras to promote lung tumorigenesis by activating NFκB and mTOR pathways via targeted degradation of tumor suppressive substrates including IκB, DEPTOR, p21 and p27.
T3 438-672 Sentence denotes Here we investigated the role of Sag/Rbx2 E3 ligase in cellular senescence and immortalization of mouse embryonic fibroblasts (MEFs) and report that Sag is required for proper cell proliferation and Kras(G12D)-induced immortalization.
T4 673-833 Sentence denotes Sag inactivation by genetic deletion remarkably suppresses cell proliferation by inducing senescence, which is associated with accumulation of p16, but not p53.
T5 834-986 Sentence denotes Mechanistically, Sag deletion caused accumulation of Jun-B, a substrate of Sag-Fbxw7 E3 ligase and a transcription factor that drives p16 transcription.
T6 987-1146 Sentence denotes Importantly, senescence triggered by Sag deletion can be largely rescued by simultaneous deletion of Cdkn2a, the p16 encoding gene, indicating its causal role.
T7 1147-1317 Sentence denotes Furthermore, Kras(G12D)-induced immortalization can also be abrogated by Sag deletion via senescence induction, which is again rescued by simultaneous deletion of Cdkn2a.
T8 1318-1476 Sentence denotes Finally, we found that Sag deletion inactivates Kras(G12D) activity and block the MAPK signaling pathway, together with accumulated p16, to induce senescence.
T9 1477-1741 Sentence denotes Taken together, our results demonstrated that Sag is a Kras(G12D)-cooperating oncogene required for Kras(G12D)-induced immortalization and transformation, and targeting SAG-SCF E3 ligase may, therefore, have therapeutic value for senescence-based cancer treatment.