Dataset Information

LFQMS of RING2 (RING1B, RNF2) immunoprecipitation from MDA-MB-231 and T47D breast cancer cells

ABSTRACT: Polycomb repressive complex PRC1 is essential for gene regulation in numerous cell fate decisions. We show that RING1B (RING2, RNF2) and canonical PRC1 (cPRC1) genes are amplified and overexpressed in breast cancer (BC). Moreover, cPRC1 complexes functionally associate with genes regulated by cell type specific key transcription factors such as estrogen receptor (ER) in ER+ tumor cells and BRD4 in triple negative BC cells. cPRC1 is recruited to active enhancers in a manner independent of PRC2 and RING1B enzymatic activity. RING1B regulates enhancer activity and gene transcription not only by promoting the expression of BC oncogenes but also by regulating chromatin accessibility for oncogenic transcription factors. RING1B recruitment, and thus PRC1 association, to active enhancers occurs in multiple cancers.

INSTRUMENT(S): Q Exactive Plus

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture, Breast Cancer Cell Line

DISEASE(S): Breast Cancer

SUBMITTER: John LaCava

LAB HEAD: John LaCava

PROVIDER: PXD009570 | Pride | 2018-10-19

REPOSITORIES: Pride

ACCESS DATA

Publications

Polycomb complexes associate with enhancers and promote oncogenic transcriptional programs in cancer through multiple mechanisms.

Chan Ho Lam HL Beckedorff Felipe F Zhang Yusheng Y Garcia-Huidobro Jenaro J Jiang Hua H Colaprico Antonio A Bilbao Daniel D Figueroa Maria E ME LaCava John J Shiekhattar Ramin R Morey Lluis L

Nature communications 20180823 1

Polycomb repressive complex 1 (PRC1) plays essential roles in cell fate decisions and development. However, its role in cancer is less well understood. Here, we show that RNF2, encoding RING1B, and canonical PRC1 (cPRC1) genes are overexpressed in breast cancer. We find that cPRC1 complexes functionally associate with ERα and its pioneer factor FOXA1 in ER+ breast cancer cells, and with BRD4 in triple-negative breast cancer cells (TNBC). While cPRC1 still exerts its repressive function, it is al ...[more]

PMID: 30139998

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Project description:Senolytic drugs are designed to selectively clear senescent cells (SnCs) that accumulate with injury or aging. In a mouse model of osteoarthritis (OA), senolysis yields a pro-regenerative response. However, recent research studies showed that the therapeutic benefit is reduced in aged mice. Increased oxidative stress (redox) mediates metabolic dysregulation and accumulation of posttranslational modifications (PTM) on proteins from the cartilage and is one of the major hallmarks of advanced age. This research investigated whether the senolytic treatment differentially affects oxidative load in the joints from young and aged animals. We employed label-free quantitative (LFQ) analysis of changes in the protein expression profiles and associated carbonylated PTMs in the extracted joint proteins. Our proteomic survey focused to a set of PTMs described as advanced glycation-end products (AGEs) or advanced lipooxidation-end products (ALEs), known to accumulate during aging and age-associated diseases. AGEs and ALEs are the result of non-enzymatic reactions of protein with reducing sugars, or with oxidized sugar or lipid degradation products, which may alter and sometimes crosslink the positively charged amino acids lysine and arginine on proteins. Our proteomic dataset supported detection of several AGEs and ALEs, including the adducts 4-ONE (4-oxononenal), 4-ONE+Delta:H(-2)O(-1) (dehydrated 4-oxononenal Michael adduct), carboxyethyl, carboxymethyl, 3-deoxyglucosone derived dihydroxyimidazoline, G-H1 (glyoxal-derived hydroimidazolone), HNE (4-hydroxynonenal), several carbonylated adducts including proline to pyrrolidinone or pyrrolidone Other detected modifications of note include mono-oxidation and di-oxidation products, including tryptophan to kynurenine. We also detected lysine-epsilon-gly-gly (GlyGly), which marks ubiquitylated sites, indicating potential substrates of proteasome-dependent degradation. The grand total PTM change was negative for treated aged OA mice but positive for treated young OA mice, regardless of whether summed across modifications or across proteins. In other words, senolytic treatment reduced oxidation associated PTMs more effectively in aged OA mice than in young OA mice. The LFQ proteomics analysis was complemented with new biophysical computational tools aimed to predict the stability of carbonylated proteins extracted from the joints. The biophysical model predicted divergent proteomic responses between young and aged animals. Altogether, our results showed that senolysis reduces overall oxidative stress in the aged arthritic joints in vivo.

Dataset Information

LFQMS of RING2 (RING1B, RNF2) immunoprecipitation from MDA-MB-231 and T47D breast cancer cells

Publications

Polycomb complexes associate with enhancers and promote oncogenic transcriptional programs in cancer through multiple mechanisms.

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