Matches in SemOpenAlex for { <https://semopenalex.org/work/W2912227322> ?p ?o ?g. }
- W2912227322 endingPage "802.e7" @default.
- W2912227322 startingPage "788" @default.
- W2912227322 abstract "mTORC1 and GSK3 play critical roles in early stages of (macro)autophagy, but how they regulate late steps of autophagy remains poorly understood. Here we show that mTORC1 and GSK3-TIP60 signaling converge to modulate autophagosome maturation through Pacer, an autophagy regulator that was identified in our recent study. Hepatocyte-specific Pacer knockout in mice results in impaired autophagy flux, glycogen and lipid accumulation, and liver fibrosis. Under nutrient-rich conditions, mTORC1 phosphorylates Pacer at serine157 to disrupt the association of Pacer with Stx17 and the HOPS complex and thus abolishes Pacer-mediated autophagosome maturation. Importantly, dephosphorylation of Pacer under nutrient-deprived conditions promotes TIP60-mediated Pacer acetylation, which facilitates HOPS complex recruitment and is required for autophagosome maturation and lipid droplet clearance. This work not only identifies Pacer as a regulator in hepatic autophagy and liver homeostasis in vivo but also reveals a signal integration mechanism involved in late stages of autophagy and lipid metabolism." @default.
- W2912227322 created "2019-02-21" @default.
- W2912227322 creator A5005975335 @default.
- W2912227322 creator A5016043975 @default.
- W2912227322 creator A5019932507 @default.
- W2912227322 creator A5031095216 @default.
- W2912227322 creator A5040523461 @default.
- W2912227322 creator A5043087920 @default.
- W2912227322 creator A5053339387 @default.
- W2912227322 creator A5056539924 @default.
- W2912227322 creator A5058965019 @default.
- W2912227322 creator A5062270234 @default.
- W2912227322 creator A5062377553 @default.
- W2912227322 creator A5066143389 @default.
- W2912227322 creator A5071037763 @default.
- W2912227322 creator A5076647931 @default.
- W2912227322 creator A5076993759 @default.
- W2912227322 creator A5082646269 @default.
- W2912227322 date "2019-02-01" @default.
- W2912227322 modified "2023-10-17" @default.
- W2912227322 title "Pacer Is a Mediator of mTORC1 and GSK3-TIP60 Signaling in Regulation of Autophagosome Maturation and Lipid Metabolism" @default.
- W2912227322 cites W1534198965 @default.
- W2912227322 cites W1534985842 @default.
- W2912227322 cites W1845621716 @default.
- W2912227322 cites W1918384196 @default.
- W2912227322 cites W1966828940 @default.
- W2912227322 cites W1970637701 @default.
- W2912227322 cites W1972986619 @default.
- W2912227322 cites W1973501203 @default.
- W2912227322 cites W1978714931 @default.
- W2912227322 cites W1981259598 @default.
- W2912227322 cites W1985124617 @default.
- W2912227322 cites W1991692801 @default.
- W2912227322 cites W1992659717 @default.
- W2912227322 cites W1994823455 @default.
- W2912227322 cites W2002671660 @default.
- W2912227322 cites W2007505836 @default.
- W2912227322 cites W2008581684 @default.
- W2912227322 cites W2009490810 @default.
- W2912227322 cites W2011014580 @default.
- W2912227322 cites W2017779665 @default.
- W2912227322 cites W2023445018 @default.
- W2912227322 cites W2026531845 @default.
- W2912227322 cites W2033212418 @default.
- W2912227322 cites W2045970460 @default.
- W2912227322 cites W2052483921 @default.
- W2912227322 cites W2053282493 @default.
- W2912227322 cites W2055654995 @default.
- W2912227322 cites W2058221507 @default.
- W2912227322 cites W2061620477 @default.
- W2912227322 cites W2063232329 @default.
- W2912227322 cites W2063620211 @default.
- W2912227322 cites W2065566367 @default.
- W2912227322 cites W2065794750 @default.
- W2912227322 cites W2065841250 @default.
- W2912227322 cites W2066697766 @default.
- W2912227322 cites W2067490363 @default.
- W2912227322 cites W2078184757 @default.
- W2912227322 cites W2078881478 @default.
- W2912227322 cites W2089695512 @default.
- W2912227322 cites W2090819513 @default.
- W2912227322 cites W2094399892 @default.
- W2912227322 cites W2094777752 @default.
- W2912227322 cites W2096308078 @default.
- W2912227322 cites W2097783258 @default.
- W2912227322 cites W2103659405 @default.
- W2912227322 cites W2111352469 @default.
- W2912227322 cites W2113432343 @default.
- W2912227322 cites W2116836791 @default.
- W2912227322 cites W2118151565 @default.
- W2912227322 cites W2119399459 @default.
- W2912227322 cites W2122826962 @default.
- W2912227322 cites W2127939726 @default.
- W2912227322 cites W2133284292 @default.
- W2912227322 cites W2133891286 @default.
- W2912227322 cites W2135453787 @default.
- W2912227322 cites W2139948451 @default.
- W2912227322 cites W2142044474 @default.
- W2912227322 cites W2146887271 @default.
- W2912227322 cites W2147058114 @default.
- W2912227322 cites W2150168624 @default.
- W2912227322 cites W2153188271 @default.
- W2912227322 cites W2155175976 @default.
- W2912227322 cites W2155810842 @default.
- W2912227322 cites W2156144699 @default.
- W2912227322 cites W2157096314 @default.
- W2912227322 cites W2171155178 @default.
- W2912227322 cites W2315925646 @default.
- W2912227322 cites W2511744821 @default.
- W2912227322 cites W2520119373 @default.
- W2912227322 cites W2562372517 @default.
- W2912227322 cites W2567875529 @default.
- W2912227322 cites W2570675177 @default.
- W2912227322 cites W2593816418 @default.
- W2912227322 cites W2595189039 @default.
- W2912227322 cites W2605743056 @default.
- W2912227322 cites W2747662156 @default.
- W2912227322 cites W2752326209 @default.