Virological and Cellular Roles of the Transcriptional Coactivator LEDGF/p75

Abstract Background To investigate the role and its potential mechanism of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4 (PFKFB4) in lung adenocarcinoma. Methods Co-immunoprecipitation was performed to analyze the interaction between PFKFB4 and SRC-2. Western blot was used to investigate the phosphorylation of steroid receptor coactivator-2 (SRC-2) on the condition that PFKFB4 was knockdown. Transcriptome sequencing was performed to find the downstream target of SRC-2. Cell Counting Kit-8 (CCK-8) assay, transwell assay and transwell-matrigel assay were used to examine the proliferation, migration and invasion abilities in A549 and NCI-H1975 cells with different treatment. Results In our study we found that PFKFB4 was overexpressed in lung adenocarcinoma associated with SRC family protein and had an interaction with SRC-2. PFKFB4 could phosphorylate SRC-2 at Ser487, which altered SRC-2 transcriptional activity. Functionally, PFKFB4 promoted lung adenocarcinoma cells proliferation, migration and invasion by phosphorylating SRC-2. Furthermore, we identified that CARM1 was transcriptionally regulated by SRC-2 and involved in PFKFB4-SRC-2 axis on lung adenocarcinoma progression. Conclusions Our research reveal that PFKFB4 promotes lung adenocarcinoma cells proliferation, migration and invasion via enhancing phosphorylated SRC-2-mediated CARM1 expression.

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YAP inhibits autophagy and promotes progression of colorectal cancer via upregulating Bcl-2 expression

Cell Death and Disease ◽

10.1038/s41419-021-03722-8 ◽

2021 ◽

Vol 12 (5) ◽

Author(s):

Lan Jin ◽

Yunhe Chen ◽

Dan Cheng ◽

Zhikai He ◽

Xinyi Shi ◽

...

Keyword(s):

Colorectal Cancer ◽

Cell Death ◽

Transcriptional Coactivator ◽

Inhibitory Protein ◽

Potential Therapeutic Target ◽

Related Cell ◽

Autophagy Inhibition

AbstractColorectal cancer (CRC) is one of the most aggressive and lethal cancers. The role of autophagy in the pathobiology of CRC is intricate, with opposing functions manifested in different cellular contexts. The Yes-associated protein (YAP), a transcriptional coactivator inactivated by the Hippo tumor-suppressor pathway, functions as an oncoprotein in a variety of cancers. In this study, we found that YAP could negatively regulate autophagy in CRC cells, and consequently, promote tumor progression of CRC in vitro and in vivo. Mechanistically, YAP interacts with TEAD forming a complex to upregulate the transcription of the apoptosis-inhibitory protein Bcl-2, which may subsequently facilitate cell survival by suppressing autophagy-related cell death; silencing Bcl-2 expression could alleviate YAP-induced autophagy inhibition without affecting YAP expression. Collectively, our data provide evidence for YAP/Bcl-2 as a potential therapeutic target for drug exploration against CRC.

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Bicyclic β‐sheet mimetics that target the transcriptional coactivator β‑catenin and inhibit Wnt signaling

Angewandte Chemie ◽

10.1002/ange.202102082 ◽

2021 ◽

Author(s):

Mathias Wendt ◽

Rosa Bellavita ◽

Alan Gerber ◽

Nina-Louisa Efrém ◽

Thirza van Ramshorst ◽

...

Keyword(s):

Wnt Signaling ◽

Transcriptional Coactivator ◽

Β Sheet

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Polycystin-2 Activity Is Controlled by Transcriptional Coactivator with PDZ Binding Motif and PALS1-associated Tight Junction Protein

Journal of Biological Chemistry ◽

10.1074/jbc.c110.146381 ◽

2010 ◽

Vol 285 (44) ◽

pp. 33584-33588 ◽

Cited By ~ 12

Author(s):

Kerstin Duning ◽

Deike Rosenbusch ◽

Marc A. Schlüter ◽

Yuemin Tian ◽

Karl Kunzelmann ◽

...

Keyword(s):

Tight Junction ◽

Tight Junction Protein ◽

Binding Motif ◽

Transcriptional Coactivator ◽

Junction Protein

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RASSF1A inhibits PDGFB-driven malignant phenotypes of nasopharyngeal carcinoma cells in a YAP1-dependent manner

Cell Death and Disease ◽

10.1038/s41419-020-03054-z ◽

2020 ◽

Vol 11 (10) ◽

Author(s):

Ying-Ying Liang ◽

Xu-Bin Deng ◽

Xian-Tao Lin ◽

Li-Li Jiang ◽

Xiao-Ting Huang ◽

...

Keyword(s):

Nasopharyngeal Carcinoma ◽

Underlying Mechanism ◽

Carcinoma Cells ◽

Dependent Manner ◽

Transcriptional Coactivator ◽

Actin Remodeling ◽

Aggressive Tumor ◽

Subunit B

Abstract Nasopharyngeal carcinoma (NPC) is a highly aggressive tumor characterized by distant metastasis. Deletion or down-regulation of the tumor suppressor protein ras-association domain family protein1 isoform A (RASSF1A) has been confirmed to be a key event in NPC progression; however, little is known about the effects or underlying mechanism of RASSF1A on the malignant phenotype. In the present study, we observed that RASSF1A expression inhibited the malignant phenotypes of NPC cells. Stable silencing of RASSF1A in NPC cell lines induced self-renewal properties and tumorigenicity in vivo/in vitro and the acquisition of an invasive phenotype in vitro. Mechanistically, RASSF1A inactivated Yes-associated Protein 1 (YAP1), a transcriptional coactivator, through actin remodeling, which further contributed to Platelet Derived Growth Factor Subunit B (PDGFB) transcription inhibition. Treatment with ectopic PDGFB partially increased the malignancy of NPC cells with transient knockdown of YAP1. Collectively, these findings suggest that RASSF1A inhibits malignant phenotypes by repressing PDGFB expression in a YAP1-dependent manner. PDGFB may serve as a potential interest of therapeutic regulators in patients with metastatic NPC.

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