PXD015326

PXD015326 is an original dataset announced via ProteomeXchange.

Title	Transcriptional regulation of FAM134B by TFEB/TFE3 controls ER-phagy in response to starvation and chondrocyte differentiation
Description	Lysosomal degradation of the endoplasmic reticulum (ER) via autophagy (ER-phagy) is emerging as a critical regulator of cell homeostasis and function1. The recent identification of ER-phagy receptors has shed light on the molecular mechanism underlining this process; however, the signaling pathways regulating ER-phagy in response to cellular needs are still largely unknown. We found that the nutrient responsive transcription factors TFEB and TFE3 - master regulators of lysosomal biogenesis and autophagy2- control ER-phagy by inducing the expression of the ER-phagy receptor FAM134B. The TFEB/TFE3-FAM134B axis promotes ER-phagy activation upon prolonged starvation. In addition, we discovered that this pathway is activated in chondrocytes by FGF signaling, a critical regulator of cell differentiation 3. FGF signaling induces a JNK-dependent proteasomal degradation of the insulin receptor substrate 1, which inhibits the insulin-PI3K-PKB/Akt-mTORC1 pathway and promotes TFEB/TFE3 nuclear translocation and FAM134B induction. Consistent with a role of the TFEB/TFE3-FAM134B axis in chondrocytes, FAM134B knock-down impairs cartilage growth and mineralization in medaka fish. This study identifies a new signaling pathway that allows ER-phagy to respond to both metabolic and developmental cues.
HostingRepository	PRIDE
AnnounceDate	2020-07-15
AnnouncementXML	Submission_2020-08-02_22:32:25.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Laura Cinque
SpeciesList	scientific name: Rattus norvegicus (Rat); NCBI TaxID: 10116;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2019-09-05 01:18:08	ID requested
1	2020-07-14 22:46:05	announced
⏵ 2	2020-08-02 22:32:26	announced	2020-08-03: Updated publication reference for PubMed record(s): 32716134.

Cinque L, De Leonibus C, Iavazzo M, Krahmer N, Intartaglia D, Salierno FG, De Cegli R, Di Malta C, Svelto M, Lanzara C, Maddaluno M, Wanderlingh LG, Huebner AK, Cesana M, Bonn F, Polishchuk E, H, ü, bner CA, 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(17):e105696(2020) [pubmed]

submitter keyword: ER-phagy, TFEB, chondrocyte, lysosome

Carmine Settembre
contact affiliation	Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, Italy Department of Translational Medicine, Federico II University , Naples , Italy
contact email	settembre@tigem.it
lab head
Laura Cinque
contact affiliation	TIGEM
contact email	l.cinque@tigem.it
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/07/PXD015326

PRIDE project URI

• PRIDE
  1. PXD015326
     1. Label: PRIDE project
     2. Name: Transcriptional regulation of FAM134B by TFEB/TFE3 controls ER-phagy in response to starvation and chondrocyte differentiation