PXD008761-1

PXD008761 is an original dataset announced via ProteomeXchange.

Title	S100A3 binds directly to RARα and the PML-RARα onco-protein modulating their stability and activit
Description	We defined the RARα interactome in the MDA-MB453 breast cancer cell line genetically engineered to over-express an N-terminally tagged version of the nuclear retinoic acid receptor. Twenty eight nuclear proteins which interact with RARα and whose interaction is stimulated or reduced by the pan-RAR ligand, all-trans retinoic acid (ATRA) were identified. Given the potential significance of the S100A3 calcium-binding protein in the control of tumor progression, we focused our attention on this factor. Using the two models represented by the ATRA-sensitive SKBR3 and MCF7 breast cancer cell lines characterized by constitutive expression of S100A3 and RARα, we demonstrate that the endogenous forms of S100A3 and RARα interact in physiological conditions. The interaction of S100A3 with RARα is cell context independent and it is observed not only in breast cancer but also in acute promyelocytioc leukemia (APL) cells, characterized by expression of the RARα-derived PML-RARα oncogene, which is the product of the t(15:17) chromosomal translocation. S100A3 interacts directly and specifically with RARα and PML-RARα, being unable to bind other members of the RAR/RXR family of retinoid nuclear receptors. The interaction surface maps to the carboxyl-terminal region of the RARα ligand binding domain. Binding of S100A3 to RARα and PML-RARα controls the constitutive and ATRA-dependent degradation of the two receptors. Silencing of the S100A3 gene decreases the amounts of RARα in breast SK-BR-3 and lung A549 cancer cells, rendering them more refractory to the anti-proliferative action of ATRA. In SK-BR-3 cells, this effect is accompanied by a decrease in the lactogenic/differentiating action of ATRA. In APL-derived NB4 cells, S100A3 knock-down reduces the amounts of both RARα and PML-RARα. Contemporaneous down-regulation of the two receptors is associated with an increase in the basal and ATRA-induced expression of many granulocytic differentiation markers. Opposite on RARα and PML-RARα levels as well as ATRA induced differentiation markers are observed upon over-expression of S100A3 in NB4 cells.
HostingRepository	PRIDE
AnnounceDate	2019-12-18
AnnouncementXML	Submission_2019-12-18_05:32:47.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Laura Brunelli
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2018-01-26 06:31:38	ID requested
⏵ 1	2019-12-18 05:32:49	announced
2	2024-10-22 04:04:52	announced	2024-10-22: Updated project metadata.

Gianni M, Terao M, Kurosaki M, Paroni G, Brunelli L, Pastorelli R, Zanetti A, Lupi M, Acquavita A, Bolis M, Fratelli M, Rochette-Egly C, Garattini E, in cellular models of breast/lung cancer and acute myeloid leukemia. Oncogene, 38(14):2482-2500(2019) [pubmed]

curator keyword: Biomedical

submitter keyword: RARalpha, interactome, SILAC

Roberta Pastorelli
contact affiliation	Laboratory of mass spectrometry, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri
contact email	roberta.pastorelli@marionegri.it
lab head
Laura Brunelli
contact affiliation	IRCCS Istituto Ricerche Farmacologiche Mario Negri
contact email	laura.brunelli@marionegri.it
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD008761
     1. Label: PRIDE project
     2. Name: S100A3 binds directly to RARα and the PML-RARα onco-protein modulating their stability and activit