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TRIM37 augments AP-2γ transcriptional activity and cellular localization via K63-linked polyubiquitination to drive breast cancer progression [RNA-seq]

ABSTRACT: Using a proteomics approach, we identified the Tripartite Motif Containing 37 (TRIM37) as a novel transcriptional coactivator of AP-2γ. We demonstrate TRIM37 facilitates AP-2γ chromatin binding to regulate the AP-2γ mediated transcriptional program directly. We provide evidence that TRIM37 achieves this by stimulating K63-chain-linked polyubiquitination of AP-2γ, promoting protein localization from the cytoplasm to the nucleus. In clinical analyses, we find TRIM37 is upregulated in multiple breast cancer datasets, supporting our findings that TRIM37-AP-2γ interaction is essential for breast cancer tumor growth. Overall, our work revealed that TRIM37 is an oncogenic coactivator of AP-2γ in breast cancer and provides a novel therapeutic target for treating the disease.

ORGANISM(S): Homo sapiens

PROVIDER: GSE182545 | GEO | 2022/07/25

REPOSITORIES: GEO

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TRIM37 augments AP-2γ transcriptional activity and cellular localization via K63-linked polyubiquitination to drive breast cancer progression [ChIP-seq]

Project description:Using a proteomics approach, we identified the Tripartite Motif Containing 37 (TRIM37) as a novel transcriptional coactivator of AP-2γ. We demonstrate TRIM37 facilitates AP-2γ chromatin binding to regulate the AP-2γ mediated transcriptional program directly. We provide evidence that TRIM37 achieves this by stimulating K63-chain-linked polyubiquitination of AP-2γ, promoting protein localization from the cytoplasm to the nucleus. In clinical analyses, we find TRIM37 is upregulated in multiple breast cancer datasets, supporting our findings that TRIM37-AP-2γ interaction is essential for breast cancer tumor growth. Overall, our work revealed that TRIM37 is an oncogenic coactivator of AP-2γ in breast cancer and provides a novel therapeutic target for treating the disease.

2022-07-25 | GSE182546 | GEO

Gene expression data from AP-2γ silenced MCF-7 cells

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Project description:Estrogen receptor α (ERα) is key player in the progression of breast cancer. ERα binds to DNA and mediates long-range chromatin interactions throughout the genome, but the underlying mechanism in this process is unclear. Here, we show that AP-2 motifs are highly enriched in the ERα binding sites (ERBS) identified from the recent ChIA-PET of ERα. More importantly, we demonstrate that AP-2γ (also known as TFAP2C), a member of the AP-2 family which has been implicated in breast cancer oncogenesis, is recruited to chromatin in a ligand-independent manner and co-localized with ERα binding events. Furthermore, pertubation of AP-2γ expression disrupts ERα DNA binding, long-range chromatin interactions, and gene transcription. Using ChIP-seq, we show that AP-2γ and ERα binding occurs in close proximity on a genome-wide scale. The majority of these shared genomic regions are also occupied by the pioneer factor, FoxA1. AP-2γ is required for efficient FoxA1 binding and vice versa. Finally, we show that most ERBS associated with long-range chromatin interactions are co-localized with both AP-2γ and FoxA1. Together, our results suggest AP-2γ is an essential factor in ERα-mediated transcription, primarily working together with FoxA1 to facilitate ERα binding and long-range chromatin interactions.

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Activator protein-2γ is a critical determinant of estrogen receptor interactome formation and gene transcription in breast cancer [ChIP-Seq]

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TRIM37 is a novel H2A ubiquitin ligase and a Breast Cancer Oncogene

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2014-10-06 | E-GEOD-48196 | biostudies-arrayexpress

AP-2γ is Required for Maintenance of Multipotent Mammary Stem Cells

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TRIM37 is a novel H2A ubiquitin ligase and a Breast Cancer Oncogene

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RNA-seq analysis of MDA-MB-231_2b cells treated with control or TRIM37 specific antisense oligonucleotides

Project description:TRIM37 is histon H2A ubiquitinase and important oncogene for breast cancer. To test what is the gene expression network regulated by TRIM37, we silenced its ixpression in MDA-MB-231_2b Triple Negative Breast Cancer (TNBC) cell line.

2022-08-31 | GSE136617 | GEO

Determination of the WWOX gene function in modulating cellular pathways activated by AP-2α and AP-2γ transcription factors in bladder cancer

Project description:The aim of the current study was to investigate how various levels of WWOX, AP-2α and AP-2γ affect signaling pathways in bladder cancer cell lines. Global transcriptome analysis using CAGE-seq was conducted.

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The ubiquitin ligase TRIM37 controls cancer-specific vulnerability to PLK4 inhibition

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