PXD026872

PXD026872 is an original dataset announced via ProteomeXchange.

Title	A YAP/TAZ-TEAD signaling module links endothelial nutrient acquisition to angiogenic growth
Description	Angiogenesis, the process by which endothelial cells (ECs) form new blood vessels from existing ones, is intimately linked to the tissue's metabolic milieu and often occurs at nutrient-deficient sites. However, ECs rely on sufficient metabolic resources to support growth and proliferation. How endothelial nutrient acquisition and usage are regulated is unknown. Here we show that these processes are dictated by YAP/TAZ-TEAD – a transcriptional module whose function is highly responsive to changes in the tissue environment. ECs lacking YAP/TAZ or their transcriptional partners, TEAD1, 2, and 4 fail to divide, resulting in stunted vascular growth in mice. Conversely, activation of TAZ, the more abundant paralogue in ECs, boosts proliferation, leading to vascular hyperplasia. We find that YAP/TAZ promote angiogenesis by fueling nutrient mTORC1 signaling. By orchestrating the transcription of a repertoire of cell-surface transporters, YAP/TAZ-TEAD stimulate the import of amino acids and other essential nutrients, thereby enabling mTORC1 pathway activation. Dissociating mTORC1 from these nutrient inputs – elicited by the loss of Rag GTPases – inhibits mTORC1 activity and prevents YAP/TAZ-dependent vascular growth. These findings define a pivotal role for YAP/TAZ-TEAD in steering endothelial mTORC1 and illustrate the essentiality of coordinated nutrient fluxes in the vasculature.
HostingRepository	PRIDE
AnnounceDate	2022-05-08
AnnouncementXML	Submission_2022-05-08_06:00:58.359.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Scientific Service Group Biomolecular Mass Spectrometry
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2021-06-22 22:59:17	ID requested
⏵ 1	2022-05-08 06:00:58	announced

Dataset with its publication pending

submitter keyword: YAP/TAZ-TEAD signaling, endothelial cells, angiogenesis, nutrient acquisition, mTORC1

Michael Potente
contact affiliation	Angiogenesis & Metabolism Laboratory, Max Planck Institut for Heart and Lung Research, 61231 Bad Nauheim, Germany
contact email	michael.potente@mpi-bn.mpg.de
lab head
Scientific Service Group Biomolecular Mass Spectrometry
contact affiliation	Max Planck Institute for Heart and Lung Research
contact email	proteomics@mpi-bn.mpg.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD026872
     1. Label: PRIDE project
     2. Name: A YAP/TAZ-TEAD signaling module links endothelial nutrient acquisition to angiogenic growth