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转化刺激克隆22（TSC-22）与含溴结构域蛋白7（BRD7）直接相互作用，以增强对卵巢癌中细胞外信号调节激酶（ERK）通路的抑制作用。

Transforming Stimulated Clone 22 (TSC-22) Interacts Directly with Bromodomain-Containing Protein 7 (BRD7) to Enhance the Inhibition of Extracellular Signal-Regulate Kinase (ERK) Pathway in Ovarian Cancer.

作者信息

Lee Seung-Hoon, Choi Donchan

机构信息

Department of Life Science, YongIn University, Yongin 17092, Korea.

出版信息

Dev Reprod. 2022 Sep;26(3):117-126. doi: 10.12717/DR.2022.26.3.117. Epub 2022 Sep 30.

DOI:10.12717/DR.2022.26.3.117
PMID:36285148
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9578317/
Abstract

Bromodomain-containing protein 7 (BRD7) participates in many cellular processes and embryo development. BRD7 is down-regulated in various cancers and evidence of its tumor suppressor function has been accumulating. Here, we identified transforming stimulated clone 22 (TSC-22) as a novel BRD7 interacting protein and show its novel function as a positive regulator of BRD7. We found that TSC-22 expression potentiated the inactivation of the extracellular signal-regulate kinase (ERK) pathway by BRD7. Our data establishes TSC-22 as a modulator of BRD7 and unravels the molecular mechanisms that drive the synergistic tumor-suppressing effects of TSC-22 and BRD7. Our findings may open new avenues for developing novel molecular therapies for tumors exhibiting down-regulated BRD7 and/or TSC-22.

摘要

含溴结构域蛋白7（BRD7）参与许多细胞过程和胚胎发育。BRD7在多种癌症中表达下调，其肿瘤抑制功能的证据也在不断积累。在此，我们鉴定出转化刺激克隆22（TSC-22）是一种新型的与BRD7相互作用的蛋白，并展示了其作为BRD7正向调节因子的新功能。我们发现TSC-22的表达增强了BRD7对细胞外信号调节激酶（ERK）途径的失活作用。我们的数据确定TSC-22为BRD7的调节剂，并揭示了驱动TSC-22和BRD7协同肿瘤抑制作用的分子机制。我们的发现可能为开发针对BRD7和/或TSC-22表达下调的肿瘤的新型分子疗法开辟新途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/383d/9578317/b83682a15aec/dr-26-3-117-g4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/383d/9578317/964587443d97/dr-26-3-117-g1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/383d/9578317/5033178ce377/dr-26-3-117-g2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/383d/9578317/87d021008e1a/dr-26-3-117-g3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/383d/9578317/b83682a15aec/dr-26-3-117-g4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/383d/9578317/964587443d97/dr-26-3-117-g1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/383d/9578317/5033178ce377/dr-26-3-117-g2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/383d/9578317/87d021008e1a/dr-26-3-117-g3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/383d/9578317/b83682a15aec/dr-26-3-117-g4.jpg

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本文引用的文献

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TSC-22 inhibits CSF-1R function and induces apoptosis in cervical cancer.TSC-22抑制集落刺激因子1受体（CSF-1R）功能并诱导宫颈癌细胞凋亡。
Oncotarget. 2017 Aug 16;8(58):97990-98003. doi: 10.18632/oncotarget.20296. eCollection 2017 Nov 17.
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The regulation of β-catenin activity and function in cancer: therapeutic opportunities.β-连环蛋白活性和功能在癌症中的调控：治疗机遇
Oncotarget. 2017 May 16;8(20):33972-33989. doi: 10.18632/oncotarget.15687.
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BRD7 Acts as a Tumor Suppressor Gene in Lung Adenocarcinoma.BRD7在肺腺癌中作为一种肿瘤抑制基因发挥作用。
PLoS One. 2016 Aug 31;11(8):e0156701. doi: 10.1371/journal.pone.0156701. eCollection 2016.
5
Tumor suppressor bromodomain-containing protein 7 cooperates with Smads to promote transforming growth factor-β responses.肿瘤抑制因子含溴结构域蛋白7与Smads协同作用以促进转化生长因子-β反应。
Oncogene. 2017 Jan 19;36(3):362-372. doi: 10.1038/onc.2016.204. Epub 2016 Jun 6.
6
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7
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