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https://www.selleckchem.com/products/pf-06826647.html WD repeat domain 77 protein (WDR77) is required for cellular proliferation of lung and prostate epithelial cells during earlier stages of development and is reactivated during prostate and lung tumorigenesis. WDR77 plays an essential role in prostate tumorigenesis and cell growth mediated by growth regulatory factors. Here, we identified E2F1 and E2F3 mRNAs as translational targets of WDR77. We demonstrated that WDR77 regulated the translation of E2F1 and E2F3 mRNAs through the 5' untranslated regions (UTRs) of E2F1 and E2F3 (E2F1/3) mRNAs. WDR77 physically interacted with programmed cell death 4 (PDCD4) that suppresses translation of mRNAs containing structured 5' UTRs by interacting with eukaryotic translation initiation factor 4A (eIF4A) and inhibiting its helicase activity. Further, we demonstrated that the interaction between WDR77 and PDCD4 prevented the binding of PDCD4 to eIF4A and relieved PDCD4's inhibitory effect on eIF4A1. Overall, our work reveals for the first time that WDR77 is directly involved in translational regulation of E2F1/3 mRNAs through their structured 5' UTRs, PDCD4, and eIF4A1 and provides novel insight into the cell growth controlled by WDR77.Human NK cells develop in tonsils through discrete NK cell developmental intermediates (NKDIs), yet the mechanistic regulation of this process is unclear. We demonstrate that Notch activation in human tonsil-derived stage 3 (CD34-CD117+CD94-NKp80-) and 4A (CD34-CD117+/-CD94+NKp80-) NKDIs promoted non-NK innate lymphoid cell differentiation at the expense of NK cell differentiation. In contrast, stage 4B (CD34-CD117+/-CD94+NKp80+) NKDIs were NK cell lineage committed despite Notch activation. Interestingly, whereas NK cell functional maturation from stage 3 and 4A NKDIs was independent of Notch activation, the latter was required for high NKp80 expression and a stage 4B-like phenotype by the NKDI-derived NK cells. The Notch-dependent effects requi

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