The LIM protein Ajuba recruits DBC1 and CBP/p300 to acetylate ERα and enhances ERα target gene expression in breast cancer cells
© The Author(s) 2018. Published by Oxford University Press on behalf of Nucleic Acids Research..
Estrogen/ERα signaling is critical for breast cancer progression and therapeutic treatments. Thus, identifying new regulators of this pathway will help to develop new therapeutics to overcome chemotherapy resistance of the breast cancer cells. Here, we report Ajuba directly interacts with ERα to potentiate ERα target gene expression, and biologically Ajuba promotes breast cancer cell growth and contributes to tamoxifen resistance of these cells. Ajuba constitutively binds the DBD and AF2 regions of ERα, and these interactions can be markedly enhanced by estrogen treatment. Mechanistically, Ajuba recruits DBC1 and CBP/p300 and forms a ternary complex to co-activate ERα transcriptional activity and concomitantly enhances ERα acetylation. Moreover, components of this complex can be found at endogenous promoters containing functional ERα responsive elements. Taken together, these data demonstrate that Ajuba functions as a novel co-activator of ERα and that Ajuba/DBC1/CBP/p300 ternary complex may be a new target for developing therapeutics to treat breast cancer.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:47 |
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| Enthalten in: |
Nucleic acids research - 47(2019), 5 vom: 18. März, Seite 2322-2335 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Xu, Beihui [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 11.10.2019 Date Revised 16.08.2021 published: Print Citation Status MEDLINE |
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| doi: |
10.1093/nar/gky1306 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM292260733 |
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| 100 | 1 | |a Xu, Beihui |e verfasserin |4 aut | |
| 245 | 1 | 4 | |a The LIM protein Ajuba recruits DBC1 and CBP/p300 to acetylate ERα and enhances ERα target gene expression in breast cancer cells |
| 264 | 1 | |c 2019 | |
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| 500 | |a Date Completed 11.10.2019 | ||
| 500 | |a Date Revised 16.08.2021 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © The Author(s) 2018. Published by Oxford University Press on behalf of Nucleic Acids Research. | ||
| 520 | |a Estrogen/ERα signaling is critical for breast cancer progression and therapeutic treatments. Thus, identifying new regulators of this pathway will help to develop new therapeutics to overcome chemotherapy resistance of the breast cancer cells. Here, we report Ajuba directly interacts with ERα to potentiate ERα target gene expression, and biologically Ajuba promotes breast cancer cell growth and contributes to tamoxifen resistance of these cells. Ajuba constitutively binds the DBD and AF2 regions of ERα, and these interactions can be markedly enhanced by estrogen treatment. Mechanistically, Ajuba recruits DBC1 and CBP/p300 and forms a ternary complex to co-activate ERα transcriptional activity and concomitantly enhances ERα acetylation. Moreover, components of this complex can be found at endogenous promoters containing functional ERα responsive elements. Taken together, these data demonstrate that Ajuba functions as a novel co-activator of ERα and that Ajuba/DBC1/CBP/p300 ternary complex may be a new target for developing therapeutics to treat breast cancer | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a AJUBA protein, human |2 NLM | |
| 650 | 7 | |a BRINP1 protein, human |2 NLM | |
| 650 | 7 | |a Cell Cycle Proteins |2 NLM | |
| 650 | 7 | |a ESR1 protein, human |2 NLM | |
| 650 | 7 | |a Estrogen Receptor alpha |2 NLM | |
| 650 | 7 | |a Estrogens |2 NLM | |
| 650 | 7 | |a LIM Domain Proteins |2 NLM | |
| 650 | 7 | |a Nerve Tissue Proteins |2 NLM | |
| 650 | 7 | |a Tumor Suppressor Proteins |2 NLM | |
| 650 | 7 | |a Tamoxifen |2 NLM | |
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| 700 | 1 | |a Li, Qi |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Ning |e verfasserin |4 aut | |
| 700 | 1 | |a Zhu, Chunxiao |e verfasserin |4 aut | |
| 700 | 1 | |a Meng, Qingrong |e verfasserin |4 aut | |
| 700 | 1 | |a Ayyanathan, Kasirajan |e verfasserin |4 aut | |
| 700 | 1 | |a Qian, Wenli |e verfasserin |4 aut | |
| 700 | 1 | |a Jia, Hao |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Jiamin |e verfasserin |4 aut | |
| 700 | 1 | |a Ni, Peihua |e verfasserin |4 aut | |
| 700 | 1 | |a Hou, Zhaoyuan |e verfasserin |4 aut | |
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