Using an in Situ Proximity Ligation Assay to Systematically Profile Endogenous Protein–Protein Interactions in a Pathway Network

Chen, Tzu Chi; Lin, Kuan Ting; Chen, Chun-Houh; Lee, Sheng An; Lee, Pei Ying; Liu, Yu Wen; Kuo, Yi Chun; Wang, Feng Sheng; Lai, Jin Mei; Huang, Chi Ying F.

doi:10.1021/pr5002737

Cited by 24 publications

(14 citation statements)

References 50 publications

(79 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We evaluated the APP and BACE1 inhibitory activities, which inhibit Ab aggregation; in addition, the matrix clearance properties of MMP-2 and MMP-9 implicated FA was actively involved in the alteration of matrix proteins and that it played a major role in in vitro extracellular matrix remodeling. As shown in a previous in situ proximity ligation assay ( in situ PLA), which is a new technique to monitor PPI with high specificity and sensitivity, it was found that APP, MMP2 and MMP9 all interacted with TGFB1, and the interaction of MMP2 and BACE1 was also positive (Chen et al, 2014 ). Furthermore, from the Human Protein Reference Database (HPRD) in the STRING platform (Higashi and Miyazaki, 2003 ), the COOH-terminal parts of APP were found to interact with the extracellular matrix and highly selectively inhibit MMP2, in which the decapeptide region of APP was likely an active site-directed inhibitor toward MMP2.…”

Section: Discussionmentioning

confidence: 86%

Application of Ferulic Acid for Alzheimer’s Disease: Combination of Text Mining and Experimental Validation

Meng

et al. 2018

Front. Neuroinform.

View full text Add to dashboard Cite

Alzheimer’s disease (AD) is an increasing concern in human health. Despite significant research, highly effective drugs to treat AD are lacking. The present study describes the text mining process to identify drug candidates from a traditional Chinese medicine (TCM) database, along with associated protein target mechanisms. We carried out text mining to identify literatures that referenced both AD and TCM and focused on identifying compounds and protein targets of interest. After targeting one potential TCM candidate, corresponding protein-protein interaction (PPI) networks were assembled in STRING to decipher the most possible mechanism of action. This was followed by validation using Western blot and co-immunoprecipitation in an AD cell model. The text mining strategy using a vast amount of AD-related literature and the TCM database identified curcumin, whose major component was ferulic acid (FA). This was used as a key candidate compound for further study. Using the top calculated interaction score in STRING, BACE1 and MMP2 were implicated in the activity of FA in AD. Exposure of SHSY5Y-APP cells to FA resulted in the decrease in expression levels of BACE-1 and APP, while the expression of MMP-2 and MMP-9 increased in a dose-dependent manner. This suggests that FA induced BACE1 and MMP2 pathways maybe novel potential mechanisms involved in AD. The text mining of literature and TCM database related to AD suggested FA as a promising TCM ingredient for the treatment of AD. Potential mechanisms interconnected and integrated with Aβ aggregation inhibition and extracellular matrix remodeling underlying the activity of FA were identified using in vitro studies.

show abstract

Section: Discussionmentioning

confidence: 86%

Application of Ferulic Acid for Alzheimer’s Disease: Combination of Text Mining and Experimental Validation

Meng

et al. 2018

Front. Neuroinform.

View full text Add to dashboard Cite

show abstract

“…Ets-1 was found to bind to Smad3 in HeLa cells 28 . In primary hepatocytes, immunofluorescence experiments were performed to show a co-localization of Ets-1 and Smad3 in the nucleus (Fig.…”

Section: Resultsmentioning

confidence: 95%

Ets-1 deficiency alleviates nonalcoholic steatohepatitis via weakening TGF-β1 signaling-mediated hepatocyte apoptosis

Wang

et al. 2019

Cell Death Dis

View full text Add to dashboard Cite

Hepatocyte apoptosis is a hallmark of nonalcoholic steatohepatitis (NASH) and contributes to liver injury, fibrosis, and inflammation. However, the molecular mechanisms underlying excessive hepatocyte apoptosis in NASH remain largely unknown. This study aimed to explore whether and how the v-ets avian erythroblastosis virus E26 oncogene homolog 1 (Ets-1) is involved in diet-induced hepatocyte apoptosis in mice. The study found that the expression level of hepatic Ets-1 was elevated in a NASH mouse model as a result of the activation of transforming growth factor beta1 (TGF-β1) signaling. In the presence of TGF-β1, phosphorylated mothers against decapentaplegic homolog 2/3 (p-Smad2/3) translocated to the binding sites of the Ets-1 promoter to upregulate the expression of Ets-1 in primary hepatocytes. In addition, Ets-1 bound directly to phosphorylated Smad3 (p-Smad3), thereby preventing the ubiquitination and proteasomal degradation of p-Smad3 and enhancing the activity of TGF-β1/Smad3 signaling. Consequently, elevated Ets-1 stimulated TGF-β1-induced hepatocyte apoptosis. However, Ets-1 knockdown alleviated diet-induced hepatocyte apoptosis and NASH with reduced liver injury, inflammation, and fibrosis. Taken together, Ets-1 had an adverse impact on hepatocyte survival under TGF-β1 treatment and accelerated the development of NASH in mice.

show abstract

“…The differential topological structures obtained through the use of different GO weighting approaches suggest that ANLN and KDR interact and create synergies in BPs and MFs, but do not share the use or functionalities of CCs. PDGFRB encodes a typical receptor tyrosine kinase, PDGFRβ, which physically interacts with PTEN according to an in situ proximity ligation assay (55). PTEN is a representative molecule in PI3K/PTEN signaling that shares the same biological pathway with ANLN (7).…”

Section: Discussionmentioning

confidence: 99%

Genetic interactions between ANLN and KDR are prognostic for breast cancer survival

et al. 2019

View full text Add to dashboard Cite

Single nucleotide polymorphisms (SNPs) are the most common genetic variation in mammalian cells with prognostic potential. Anillin-actin binding protein (ANLN) has been identified as being involved in PI3K/PTEN signaling, which is critical in cell life/death control, and kinase insert domain receptor (KDR) encodes a key receptor mediating the cancer angiogenesis/metastasis switch. Knowledge of the intrinsic connections between PI3K/PTEN and KDR signaling, which represent two critical transitions in carcinogenesis, led the present study to investigate the effects of the potential synergy between ANLN and KDR on breast cancer outcome and identify relevant SNPs driving such a synergy at the genetic level. The survival associations of SNPs from KDR and ANLN were assessed through pairwise interaction survival analysis, quantitative trait loci analysis, pathway enrichment analysis and network construction, and the interactions between ANLN and KDR were validated in vitro. It was found that both rare homozygotes in the ANLN:rs12535394 and KDR:rs11133360 SNP pair are prognostic of favorable breast cancer survival and underpin the prominent roles of the immune response in cancer state control. This study contributes to breast cancer prognosis and therapeutic design by providing genetic evidence of interactions between ANLN and KDR, and suggesting the prominent role of the immune response in driving the synergies between the cancer cell life/death and angiogenesis/metastasis transitions during carcinogenesis.

show abstract

Using an in Situ Proximity Ligation Assay to Systematically Profile Endogenous Protein–Protein Interactions in a Pathway Network

Cited by 24 publications

References 50 publications

Application of Ferulic Acid for Alzheimer’s Disease: Combination of Text Mining and Experimental Validation

Application of Ferulic Acid for Alzheimer’s Disease: Combination of Text Mining and Experimental Validation

Ets-1 deficiency alleviates nonalcoholic steatohepatitis via weakening TGF-β1 signaling-mediated hepatocyte apoptosis

Genetic interactions between ANLN and KDR are prognostic for breast cancer survival

Contact Info

Product

Resources

About