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Cinque, L.* ; De Leonibus, C.* ; Iavazzo, M.* ; Krahmer, N. ; Intartaglia, D.* ; Salierno, F.G.* ; De Cegli, R.* ; Di Malta, C.* ; Svelto, M.* ; Lanzara, C.* ; Maddaluno, M.* ; Wanderlingh, L.G.* ; Huebner, A.K.* ; Cesana, M.* ; Bonn, F.* ; Polishchuk, E.* ; Hübner, C.A.* ; Conte, I.* ; Dikic, I.* ; Mann, M.* ; Ballabio, A.* ; Sacco, F.* ; Grumati, P.* ; Settembre, C.*

MiT/TFE factors control ER-phagy via transcriptional regulation of FAM134B.

EMBO J. 39:e105696 (2020)
Verlagsversion DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
Lysosomal degradation of the endoplasmic reticulum (ER) via autophagy (ER-phagy) is emerging as a critical regulator of cell homeostasis and function. The recent identification ofER-phagy receptors has shed light on the molecular mechanisms underlining this process. However, the signaling pathways regulatingER-phagy in response to cellular needs are still largely unknown. We found that the nutrient responsive transcription factorsTFEBandTFE3-master regulators of lysosomal biogenesis and autophagy-controlER-phagy by inducing the expression of theER-phagy receptorFAM134B. TheTFEB/TFE3-FAM134B axis promotesER-phagy activation upon prolonged starvation. In addition, this pathway is activated in chondrocytes byFGFsignaling, a critical regulator of skeletal growth.FGFsignaling inducesJNK-dependent proteasomal degradation of the insulin receptor substrate 1 (IRS1), which in turn inhibits thePI3K-PKB/Akt-mTORC1 pathway and promotesTFEB/TFE3 nuclear translocation and enhancesFAM134B transcription. Notably,FAM134B is required for protein secretion in chondrocytes, and cartilage growth and bone mineralization in medaka fish. This study identifies a new signaling pathway that allowsER-phagy to respond to both metabolic and developmental cues.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Er-phagy ; Fam134b ; Fgfsignaling ; Irs1 ; Pi3k Signaling ; Tfeb; Endoplasmic-reticulum; Bone-growth; Er-phagy; Autophagy; Receptor; Mtorc1; Mechanism; Network; Tex264; Fgf
ISSN (print) / ISBN 0261-4189
e-ISSN 1460-2075
Zeitschrift EMBO Journal, The
Quellenangaben Band: 39, Heft: 17, Seiten: , Artikelnummer: e105696 Supplement: ,
Verlag Wiley
Verlagsort Heidelberg, Germany
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes and Obesity (IDO)
Förderungen Associazione Italiana per la Ricerca sul Cancro (AIRC)
European Research Council (ERC)