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

Cinque, L., De Leonibus, C., Iavazzo, M., Krahmer, N., Intartaglia, D., Salierno, F. G., et al. (2020). MiT/TFE factors control ER-phagy via transcriptional regulation of FAM134B. EMBO Journal, 39(17): e105696. doi:10.15252/embj.2020105696.

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 Creators:
Cinque, Laura1, Author
De Leonibus, Chiara1, Author
Iavazzo, Maria1, Author
Krahmer, Natalie2, Author           
Intartaglia, Daniela1, Author
Salierno, Francesco Giuseppe1, Author
De Cegli, Rossella1, Author
Di Malta, Chiara1, Author
Svelto, Maria1, Author
Lanzara, Carmela1, Author
Maddaluno, Marianna1, Author
Wanderlingh, Luca Giorgio1, Author
Huebner, Antje K.1, Author
Cesana, Marcella1, Author
Bonn, Florian1, Author
Polishchuk, Elena1, Author
Huebner, Christian A.1, Author
Conte, Ivan1, Author
Dikic, Ivan1, Author
Mann, Matthias2, Author           
Ballabio, Andrea1, AuthorSacco, Francesca1, AuthorGrumati, Paolo1, AuthorSettembre, Carmine1, Author more..
Affiliations:
1external, ou_persistent22              
2Mann, Matthias / Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565159              

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Free keywords: ENDOPLASMIC-RETICULUM; BONE-GROWTH; ER-PHAGY; AUTOPHAGY; RECEPTOR; MECHANISM; NETWORK; TEX264; FGFBiochemistry & Molecular Biology; Cell Biology; ER-phagy; Fam134B; FGFsignaling; IRS1; PI3K signaling; TFEB;
 Abstract: 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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Language(s): eng - English
 Dates: 2020
 Publication Status: Published online
 Pages: 22
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: ISI: 000566991800007
DOI: 10.15252/embj.2020105696
 Degree: -

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Title: EMBO Journal
  Other : EMBO J.
Source Genre: Journal
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Publ. Info: Nature Publishing Group
Pages: - Volume / Issue: 39 (17) Sequence Number: e105696 Start / End Page: - Identifier: ISSN: 0261-4189
CoNE: https://pure.mpg.de/cone/journals/resource/954925497061