Molecular cell, 2014-10, Vol.56 (2), p.261-274
2014
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- Autor(en) / Beteiligte
- Titel
- Modification of ASC1 by UFM1 Is Crucial for ERα Transactivation and Breast Cancer Development
- Ist Teil von
- Molecular cell, 2014-10, Vol.56 (2), p.261-274
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2014
- Quelle
- ScienceDirect Pay Per View(PPV) Titles
- Beschreibungen/Notizen
- Biological roles for UFM1, a ubiquitin-like protein, are largely unknown, and therefore we screened for targets of ufmylation. Here we show that ufmylation of the nuclear receptor coactivator ASC1 is a key step for ERα transactivation in response to 17β-estradiol (E2). In the absence of E2, the UFM1-specific protease UfSP2 was bound to ASC1, which maintains ASC1 in a nonufmylated state. In the presence of E2, ERα bound ASC1 and displaced UfSP2, leading to ASC1 ufmylation. Polyufmylation of ASC1 enhanced association of p300, SRC1, and ASC1 at promoters of ERα target genes. ASC1 overexpression or UfSP2 knockdown promoted ERα-mediated tumor formation in vivo, which could be abrogated by treatment with the anti-breast cancer drug tamoxifen. In contrast, expression of ufmylation-deficient ASC1 mutant or knockdown of the UFM1-activating E1 enzyme UBA5 prevented tumor growth. These findings establish a role for ASC1 ufmylation in breast cancer development by promoting ERα transactivation. [Display omitted] •17β-estradiol induces ASC1 modification by poly-UFM1 chains (ufmylation)•Poly-UFM1 chains recruit ASC1, p300, and SRC1 to the promoters of ERα target genes•ASC1 ufmylation promotes cell growth and tumor formation by ERα transactivation•ASC1 ufmylation plays a crucial role in development of ERα-positive breast cancer UFM1 is the most recently identified ubiquitin-like protein, but its biological roles are largely unknown. Yoo et al. show that ASC1 modification by UFM1 plays a crucial role in breast cancer development by promoting the recruitment of ASC1, p300, and SRC1 to promoters of ERα target genes.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1097-2765eISSN: 1097-4164DOI: 10.1016/j.molcel.2014.08.007Titel-ID: cdi_proquest_miscellaneous_1622059447
- Format
- –
- Schlagworte
- Amino Acid Transport System y+ - chemistry, Amino Acid Transport System y+ - genetics, Amino Acid Transport System y+ - metabolism, Animals, Breast Neoplasms - metabolism, Breast Neoplasms - pathology, Carrier Proteins - metabolism, Cell Line, Tumor, Cysteine Endopeptidases - metabolism, E1A-Associated p300 Protein - genetics, Enzyme Activation - genetics, Estradiol - genetics, Estradiol - metabolism, Estrogen Antagonists - pharmacology, Estrogen Receptor alpha - genetics, Estrogen Receptor alpha - metabolism, Female, HEK293 Cells, Humans, MCF-7 Cells, Mice, Mice, Nude, Nuclear Receptor Coactivator 1 - genetics, Promoter Regions, Genetic - genetics, Protein Binding - genetics, Proteins - chemistry, Proteins - metabolism, Tamoxifen - pharmacology, Transcriptional Activation, Ubiquitin - metabolism, Ubiquitin-Activating Enzymes - genetics, Ubiquitin-Protein Ligases - metabolism