PXD015130

PXD015130 is an original dataset announced via ProteomeXchange.

Title	MiT/TFE factors control ER-phagy via transcriptional regulation of FAM134B
Description	Lysosomal degradation of the endoplasmic reticulum (ER) via autophagy (ER-phagy) is emerging as a critical regulator of ER homeostasis and function1. The selective incorporation of ER fragments into nascent autophagosomes is facilitated by ER resident proteins, ER-phagy receptors, that bind the autophagosomal LC3 protein via the cytosolic LC3 interacting domain (LIR) (REF). However, the molecular mechanisms that regulate ER-phagy in response to cellular needs are still largely unknown. We found that the MiT/TFE transcription factors - master regulators of lysosomal biogenesis and autophagy2- control ER-phagy by inducing the expression of the ER-phagy receptor FAM134B. This pathway is robustly activated in chondrocytes by FGF signaling, a critical regulator of chondrocyte differentiation3. FGF triggers TFEB/TFE3-mediated ER-phagy through JNK-dependent proteasomal degradation of the insulin receptor substrate 1 (IRS-1) protein and inhibition of the insulin signaling. FAM134B knock-down impairs cartilage growth and mineralization in medaka fish, suggesting a physiological role for this process during skeletal growth. Notably, we showed that the TFEB/TFE3-FAM134B axis promotes ER-phagy activation upon prolonged starvation. Thus, this study identifies MiT/TFE-factors as key transcriptional activators of ER-phagy in response to both metabolic and developmental cues.
HostingRepository	PRIDE
AnnounceDate	2020-07-15
AnnouncementXML	Submission_2020-08-02_22:35:01.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Florian Bonn
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	2019-08-22 03:04:16	ID requested
1	2020-07-14 22:38:19	announced
⏵ 2	2020-08-02 22:35:02	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]

curator keyword: Biological

submitter keyword: Erphagy Secretome

Carmine Settembre
contact affiliation	Cell Biology and Disease Mechanisms, TeleThon Institute of Genetics and Medicine
contact email	settembre@tigem.it
lab head
Florian Bonn
contact affiliation	University of Frankfurt
contact email	flobonn@gmail.com
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/PXD015130

PRIDE project URI

• PRIDE
  1. PXD015130
     1. Label: PRIDE project
     2. Name: MiT/TFE factors control ER-phagy via transcriptional regulation of FAM134B