PXD029136-1

PXD029136 is an original dataset announced via ProteomeXchange.

Title	Role of the E3 Ubiquitin-ligase Hakai in intestinal inflammation and cancer bowel disease
Description	E3 ubiquitin-ligases are important for the cellular protein homeostasis and their deregulation is implicated in cancer. The E3 ubiquitin-ligase Hakai is involved in tumour progression and metastasis, through the regulation of the tumour suppressor E-cadherin. Hakai is overexpressed in colon cancer, however, the implication in colitis-associated cancer is unknown. Here, we investigated the potential role of Hakai in intestinal inflammation and cancer bowel disease.Several mouse models of colitis and associated cancer were used including AOM-DSS, acute colitis, and genetically modified mice deficient for the IL-10 gene, to analyse Hakai expression by immunohistochemistry. Interactome analysis of Hakai was performed and effect on selected protein was determined by plasmid and siRNA transfection, western-blotting, immunoprecipitation, immunofluorescence and ubiquitination assays. Lipid accumulation was assayed by oil red staining. Immunohistochemistry was also performed in inflamed colon biopsies from ulcerative colitis, Crohn's disease and colorectal cancer patients. Our results show that Hakai was downregulated in inflammatory tissues in different mouse models. Fatty Acid Synthase (FASN) protein was identified as a novel Hakai-interacting protein. Hakai induces FASN ubiquitination and degradation via lysosome, thus regulating FASN-mediated lipid accumulation. An inverse expression of FASN with Hakai expression was detected in inflammatory AOM/DSS mouse model. In conclusion, Hakai regulates FASN ubiquitination and degradation, resulting in the regulation of FASN-mediated lipid accumulation, which is associated to the development of inflammatory bowel disease. The interaction between Hakai and FASN may be an important mechanism for the homeostasis of intestinal barrier function and in the pathogenesis of this disease.
HostingRepository	PRIDE
AnnounceDate	2022-10-25
AnnouncementXML	Submission_2022-10-25_02:51:00.764.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	SusanaBravo
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	TripleTOF 6600

Revision	Datetime	Status	ChangeLog Entry
0	2021-10-14 08:21:52	ID requested
⏵ 1	2022-10-25 02:51:01	announced
2	2023-11-14 08:54:13	announced	2023-11-14: Updated project metadata.

submitter keyword: intestinal inflammation and cancer bowel disease,E3 ubiquitin-ligase Hakai, FASN

Susana B BravoLopez
contact affiliation	Instituto de Investigaciones Sanitarias de Santiago de Compostela
contact email	sbbravo@gmail.com
lab head
SusanaBravo
contact affiliation	FIDIS
contact email	sbbravo@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD029136
     1. Label: PRIDE project
     2. Name: Role of the E3 Ubiquitin-ligase Hakai in intestinal inflammation and cancer bowel disease