PXD021462

PXD021462 is an original dataset announced via ProteomeXchange.

Title	Proteomic analyses identify ANP32A and CAND1 as androgen receptor and splice variant coactivators, whose interactions are regulated by DNA-dependent protein kinase
Description	ARv7, the most prevalent androgen receptor (AR) variant in castration resistant prostate cancer (CRPC), lacks the AR ligand binding domain (LBD) making it resistant to LBD-targeting pharmacological inhibitors, such as enzalutamide. Identifying new prostate cancer therapeutic targets by defining key coregulators (CoRs) and associated regulatory enzymes that govern AR and ARv7 transcriptional activity is critically needed. Here, we have developed a cell-free DNA pulldown assay employing androgen response elements (AREs) to isolate and characterize the AR/ARv7 CoR complexes formed on DNA. Mass spectrometry analyses of ARE pulldowns revealed previously undescribed AR and ARv7 interacting coregulators. ARv7 has enhanced recruitment of a subset of AR interacting CoRs, such as ANP32A and CAND1. SMRT, a known AR corepressor, is recruited with AR in the presence of androgens, but not with ARv7. Knockdown of ANP32A or CAND1 in prostate cancer cells reduced the expression of AR and ARv7 target gene expression, suggesting they function as coactivators. Bioinformatic analyses in human prostate cancer clinical datasets revealed that ANP32A and CAND1 expressions correlated with metastatic prostate cancer, poorer patient prognosis, and increased risk of recurrence. Additionally, DNA-dependent protein kinase (DNA-PK) was identified as an enzyme that directly phosphorylates AR and ARv7 and coactivates their transcriptional activities. DNA-PK action also stabilizes the interactions of ANP32A and CAND1 with AR and ARv7 complexes. Collectively, these findings suggest that DNA-PK coactivates the AR and ARv7 CoR complexes through its enzymatic function and by stabilizing the interaction of coactivators such as ANP32A and CAND1. Loss of SMRT recruitment combined with enhanced interaction of coactivators may contribute to unregulated ARv7 hyperactivity. Therefore, combination therapeutic approaches targeting AR/ARv7, DNA-PK, and ANP32A/CAND1 may lead to improved patient prognosis and novel prostate cancer treatment strategies.
HostingRepository	PRIDE
AnnounceDate	2026-04-06
AnnouncementXML	Submission_2026-04-06_13:06:07.963.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Bhoomi Bhatt
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	monohydroxylated residue; deamidated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2020-09-14 02:07:55	ID requested
⏵ 1	2026-04-06 13:06:08	announced

Dataset with its publication pending

submitter keyword: Prostate cancer, coregulators, and CAND1, DNA-dependent protein kinase,Androgen receptor, Androgen receptor splice variant, ANP32A

Ross Hamilton
contact affiliation	Baylor College of Medicine
contact email	ross.hamilton@bcm.edu
lab head
Bhoomi Bhatt
contact affiliation	Baylor College of Medicine
contact email	bbhatt@bcm.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD021462
     1. Label: PRIDE project
     2. Name: Proteomic analyses identify ANP32A and CAND1 as androgen receptor and splice variant coactivators, whose interactions are regulated by DNA-dependent protein kinase