PXD045048-1

PXD045048 is an original dataset announced via ProteomeXchange.

Title	The p53 Tumor Suppressor Regulates AKR1B1 Expression, a MetastasisPromoting Gene in Breast Cancer
Description	Alteration of metabolism in cancer cells is a central aspect of the mechanisms that sustain aggressive traits. Aldo-keto reductase 1 B1 (AKR1B1) catalyzes the reduction of several aldehydes to alcohols consuming NADPH. Nevertheless, the ability of AKR1B1 to reduce different substrates renders difficult to comprehensively ascertain its biological role. Recent evidence has implicated AKR1B1 in cancer, however, the mechanisms underlying its pro-oncogenic function remain largely unknown. In this work, we report that AKR1B1 expression is controlled by the p53 tumor suppressor. We found that breast cancer patients bearing wild type TP53 have reduced AKR1B1 expression. In cancer cell lines, p53 reduced AKR1B1 mRNA and protein levels, and repressed promoter activity in luciferase assays. Furthermore, chromatin immunoprecipitation assays indicated that p53 is recruited to the AKR1B1 promoter. We also observed that AKR1B1 overexpression promoted metastasis in the 4T1 orthotopic model of triple negative breast cancer. Proteomic analysis of 4T1 cells overexpressing AKR1B1 showed that AKR1B1 exerts a marked effect on proteins related to metabolism, with particular impact on mitochondrial function. This work provides novel insights on the link between the p53 pathway and metabolism in cancer cells and contributes to characterizing the alterations associated to the pathologic role of AKR1B1.
HostingRepository	PRIDE
AnnounceDate	2023-09-19
AnnouncementXML	Submission_2023-09-18_19:21:03.753.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	GermánRosano
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2023-09-02 09:02:55	ID requested
⏵ 1	2023-09-18 19:21:04	announced
2	2023-11-14 09:01:21	announced	2023-11-14: Updated project metadata.
3	2024-10-22 06:03:23	announced	2024-10-22: Updated project metadata.

submitter keyword: breast cancer, Mitochondria, electron transport chain, aldo-keto reductases,AKR1B1, Proteomics, p53, metastasis

GermánRosano
contact affiliation	Instituto de Biología Molecular y Celular de Rosario, IBR,CONICET-UNR
contact email	rosano@ibr-conicet.gov.ar
lab head
GermánRosano
contact affiliation	Instituto de Biología Molecular y Celular de Rosario (IBR-CONICET-UNR)
contact email	rosano@ibr-conicet.gov.ar
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD045048
     1. Label: PRIDE project
     2. Name: The p53 Tumor Suppressor Regulates AKR1B1 Expression, a MetastasisPromoting Gene in Breast Cancer