PXD034909

PXD034909 is an original dataset announced via ProteomeXchange.

Title	An AIB1 isoform rewires glucocorticoid receptor signaling to promote TNBC progression
Description	NCOA3, also known as the oncogene AIB1 (Amplified in Breast Cancer-1), is the third member of the p160 family of steroid receptor coactivators (SRC3). Using global alignment, we show that the genomic architecture of NCOA3/AIB1 is conserved across vertebrate and invertebrate species between exon 3 and the 3’UTR. In particular, the N-terminal domain is highly conserved with a cophenetic distance <2 between mouse and human. Interestingly, in both species the degree of exon skipping in this region between exons 3-10 is significantly higher than the rest of the gene. We have previously reported a naturally occurring mRNA isoform of human NCOA3/AIB1 that is generated by skipping of exon 4 (AIB1∆4) resulting in an N-terminally truncated protein missing the bHLH-PAS domain. AIB1∆4 is a potent transcriptional coactivator overexpressed in some human cancers and can increase their invasive potential. Here we report that in contrast to exon 4 skipping in human transcripts, murine mRNA showed recurrent skipping of exon 5 (AIB1∆5), especially in spleen and immune T and B cells, producing a protein with a similar mass to that of human AIB1∆4. Mass spectrometry confirmed that murine AIB1∆5 has an acetylated N-terminal start site 11 amino acids upstream of the start site of human AIB1∆4. We found that murine AIB1∆5 expression increases during malignant progression of tumors and is a potent coactivator of nuclear receptor transcriptional activity. Thus, our data indicate that the N-terminal region of NCOA3/AIB1 is a conserved “hot spot” of alternative splicing that modulates its activity.
HostingRepository	PRIDE
AnnounceDate	2026-01-16
AnnouncementXML	Submission_2026-01-16_07:44:56.245.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD034909
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Junfeng Ma
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2022-06-26 07:39:31	ID requested
⏵ 1	2026-01-16 07:44:56	announced

10.6019/PXD034909;

submitter keyword: None

Junfeng Ma
contact affiliation	Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington DC 20007, USA
contact email	JM3004@georgetown.edu
lab head
Junfeng Ma
contact affiliation	Georgetown University Medical Center
contact email	jm3004@georgetown.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD034909
     1. Label: PRIDE project
     2. Name: An AIB1 isoform rewires glucocorticoid receptor signaling to promote TNBC progression