PXD048587-1

PXD048587 is an original dataset announced via ProteomeXchange.

Title	EFHD2 Suppresses Intestinal Inflammation by Blocking Intestinal Epithelial Cell TNFR1 Internalization and Cell Death
Description	Death of intestinal epithelial cells (IECs) is important in the pathological process of intestinal inflammatory diseases. TNF acts as one pathogenic driver for inducing IEC death and substantial intestinal inflammation. However, the physiological protective mechanisms for suppressing TNF-induced IEC death remain poorly understood. Here, we report that EF-hand domain-containing protein D2 (EFHD2), highly expressed in normal intestine tissues but decreased in intestinal biopsy samples of ulcerative colitis patients, protects the intestinal epithelium from TNF-induced IEC apoptosis. EFHD2 inhibits TNF-induced apoptosis in primary IECs and intestinal organoids (enteroids). Mice deficient of Efhd2 in IECs exhibit excessive IEC death and exacerbated experimental colitis. Mechanistically, EFHD2 interacts with Cofilin to suppress the phosphorylation of Cofilin, leading to the inhibition of TNF receptor Ⅰ (TNFR1) internalization and TNF-induced apoptosis. Our findings define EFHD2 as an endogenous suppressor of IEC death to protect intestine inflammation, providing new insight to the regulation of death receptor signaling and control of intestinal inflammatory diseases.
HostingRepository	iProX
AnnounceDate	2024-01-14
AnnouncementXML	Submission_2024-01-15_21:07:25.577.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jiacheng Wu
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2024-01-15 21:07:14	ID requested
⏵ 1	2024-01-15 21:07:25	announced

Dataset with its publication pending

submitter keyword: Intestinal inflammation, EF-hand domain-containing protein D2, Inflammatory bowel disease, Epithelial cell death, TNFR1 internalization

Xuetao Cao
contact affiliation	Department of Immunology, Institute of Basic Medical Sciences, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing
contact email	caoxt@immunol.org
lab head
Jiacheng Wu
contact affiliation	Peking Union Medical College, Chinese Academy of Medical Sciences
contact email	jiachengwu_immunol@outlook.com
dataset submitter

iProX dataset URI