IndraLab

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OTUD7B activates mTORC2. 5 / 5
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"As such it would be expected that both CUL4B-DDB1 and TRAF2 enhance mTORC1 dependent S6K and 4E-BP1 phosphorylation while UCH-L1 and OTUD7B enhance mTORC2 dependent AKT phosphorylation at S473.mTOR si[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"For example, OTUD7B activates mTORC2 by deubiquitinating and removing polyubiquitin chains from GβL, promoting its interaction with SIN1, which enhances AKT signaling and thereby contributes to lung tumorigenesis [ xref ]."
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"mTOR is the catalytic subunit of two complexes, mTORC1 and mTORC2.65 mTORC1 comprises mTOR, a regulatory protein associated with mTOR (Raptor) and mammalian lethal with Sec13 protein 8 (mLST8, also referred to as GβL).65 In contrast, mTORC2 comprises mTOR, rapamycin insensitive companion of mTOR (Rictor), and GβL.65 Otud7b has been reported to promote mTORC2 signaling through the deubiquitination of GβL."
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"Given that binding of p110alpha subunit to Ras and subsequent activation of PI3K is required for the development and maintenance of Kras driven lung tumours XREF_BIBR, XREF_BIBR, we further assessed whether Otud7b promoted mTORC2 and Akt signalling is causally related to Kras induced lung tumorigenesis."
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"Pathologically, OTUD7B mediated activation of mTORC2 and AKT signalling may be a critical molecular event down-stream of the RAS and PI3K pathway to favour Kras LA2 -driven lung tumorigenesis, suggesting that OTUD7B may be a potential therapeutic target against diseases harbouring hyperactivated PI3K and mTOR signalling such as cancer."
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