Matches in SemOpenAlex for { <https://semopenalex.org/work/W2974606989> ?p ?o ?g. }
- W2974606989 endingPage "5599" @default.
- W2974606989 startingPage "5584" @default.
- W2974606989 abstract "The microphthalmia family of transcription factors (MiT/TFEs) controls lysosomal biogenesis and is negatively regulated by the nutrient sensor mTORC1. However, the mechanisms by which cells with constitutive mTORC1 signaling maintain lysosomal catabolism remain to be elucidated. Using the murine epidermis as a model system, we found that epidermal Tsc1 deletion resulted in a phenotype characterized by wavy hair and curly whiskers, and was associated with increased EGFR and HER2 degradation. Unexpectedly, constitutive mTORC1 activation with Tsc1 loss increased lysosomal content via upregulated expression and activity of MiT/TFEs, whereas genetic deletion of Rheb or Rptor or prolonged pharmacologic mTORC1 inactivation had the reverse effect. This paradoxical increase in lysosomal biogenesis by mTORC1 was mediated by feedback inhibition of AKT, and a resulting suppression of AKT-induced MiT/TFE downregulation. Thus, inhibiting hyperactive AKT signaling in the context of mTORC1 loss-of-function fully restored MiT/TFE expression and activity. These data suggest that signaling feedback loops work to restrain or maintain cellular lysosomal content during chronically inhibited or constitutively active mTORC1 signaling, respectively, and reveal a mechanism by which mTORC1 regulates upstream receptor tyrosine kinase signaling." @default.
- W2974606989 created "2019-09-26" @default.
- W2974606989 creator A5001595844 @default.
- W2974606989 creator A5003076340 @default.
- W2974606989 creator A5005380050 @default.
- W2974606989 creator A5008552473 @default.
- W2974606989 creator A5014074616 @default.
- W2974606989 creator A5014396784 @default.
- W2974606989 creator A5047183440 @default.
- W2974606989 creator A5047964587 @default.
- W2974606989 creator A5054599689 @default.
- W2974606989 creator A5063236475 @default.
- W2974606989 creator A5073562417 @default.
- W2974606989 creator A5073595083 @default.
- W2974606989 creator A5079019104 @default.
- W2974606989 creator A5087756231 @default.
- W2974606989 date "2019-11-11" @default.
- W2974606989 modified "2023-10-17" @default.
- W2974606989 title "mTORC1 feedback to AKT modulates lysosomal biogenesis through MiT/TFE regulation" @default.
- W2974606989 cites W139613233 @default.
- W2974606989 cites W1678795445 @default.
- W2974606989 cites W1869023438 @default.
- W2974606989 cites W1965626427 @default.
- W2974606989 cites W1969342645 @default.
- W2974606989 cites W1970944257 @default.
- W2974606989 cites W1972036696 @default.
- W2974606989 cites W1972752359 @default.
- W2974606989 cites W1974178287 @default.
- W2974606989 cites W1975200363 @default.
- W2974606989 cites W1984412362 @default.
- W2974606989 cites W1987944936 @default.
- W2974606989 cites W1996992012 @default.
- W2974606989 cites W2002583936 @default.
- W2974606989 cites W2008744347 @default.
- W2974606989 cites W2009966467 @default.
- W2974606989 cites W2017779665 @default.
- W2974606989 cites W2021207380 @default.
- W2974606989 cites W2022812113 @default.
- W2974606989 cites W2035510998 @default.
- W2974606989 cites W2041515888 @default.
- W2974606989 cites W2046447620 @default.
- W2974606989 cites W2047754866 @default.
- W2974606989 cites W2071749956 @default.
- W2974606989 cites W2077418979 @default.
- W2974606989 cites W2078184757 @default.
- W2974606989 cites W2090739159 @default.
- W2974606989 cites W2094399892 @default.
- W2974606989 cites W2094630875 @default.
- W2974606989 cites W2108360575 @default.
- W2974606989 cites W2108541764 @default.
- W2974606989 cites W2113913169 @default.
- W2974606989 cites W2116505693 @default.
- W2974606989 cites W2119748249 @default.
- W2974606989 cites W2124946605 @default.
- W2974606989 cites W2131856428 @default.
- W2974606989 cites W2138035159 @default.
- W2974606989 cites W2139948451 @default.
- W2974606989 cites W2153188271 @default.
- W2974606989 cites W2157983986 @default.
- W2974606989 cites W2160200374 @default.
- W2974606989 cites W2164613605 @default.
- W2974606989 cites W2214198121 @default.
- W2974606989 cites W2305435220 @default.
- W2974606989 cites W2339005651 @default.
- W2974606989 cites W2413006966 @default.
- W2974606989 cites W2480678377 @default.
- W2974606989 cites W2520973513 @default.
- W2974606989 cites W2528951642 @default.
- W2974606989 cites W2565398910 @default.
- W2974606989 cites W2587142564 @default.
- W2974606989 cites W2593816418 @default.
- W2974606989 cites W2626522201 @default.
- W2974606989 cites W2734333850 @default.
- W2974606989 cites W2739830864 @default.
- W2974606989 cites W2741865238 @default.
- W2974606989 cites W2758602390 @default.
- W2974606989 cites W2787534408 @default.
- W2974606989 cites W2792155253 @default.
- W2974606989 cites W2803875384 @default.
- W2974606989 cites W2898001543 @default.
- W2974606989 cites W2949603991 @default.
- W2974606989 doi "https://doi.org/10.1172/jci128287" @default.
- W2974606989 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6877313" @default.
- W2974606989 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/31527310" @default.
- W2974606989 hasPublicationYear "2019" @default.
- W2974606989 type Work @default.
- W2974606989 sameAs 2974606989 @default.
- W2974606989 citedByCount "18" @default.
- W2974606989 countsByYear W29746069892020 @default.
- W2974606989 countsByYear W29746069892021 @default.
- W2974606989 countsByYear W29746069892022 @default.
- W2974606989 countsByYear W29746069892023 @default.
- W2974606989 crossrefType "journal-article" @default.
- W2974606989 hasAuthorship W2974606989A5001595844 @default.
- W2974606989 hasAuthorship W2974606989A5003076340 @default.
- W2974606989 hasAuthorship W2974606989A5005380050 @default.
- W2974606989 hasAuthorship W2974606989A5008552473 @default.
- W2974606989 hasAuthorship W2974606989A5014074616 @default.