Chapter 14 Functional Characterization of a Mitochondrial Ser/Thr Protein Phosphatase in Cell Death Regulation

Background: (1-(2-hydroxy-5-nitrophenyl)(4-hydroxyphenyl)methyl)indoline-4-carbonitrile (HIC), an agonist of the P2Y1 receptor (P2Y1R), induces cell death in prostate cancer cells. However, the molecular mechanism behind the inhibition of HIC in prostate cancer remains elusive. Methods and results: Here, to outline the inhibitory role of HIC on prostate cancer cells, PC-3 and DU145 cell lines were treated with the respective IC50 concentrations, which reduced cell proliferation, adherence properties and spheroid formation. HIC was able to arrest the cell cycle at G1/S phase and also induced apoptosis and DNA damage, validated by gene expression profiling. HIC inhibited the prostate cancer cells’ migration and invasion, revealing its antimetastatic ability. P2Y1R-targeted HIC affects p53, MAPK and NF-κB protein expression, thereby improving the p53 stabilization essential for G1/S arrest and cell death. Conclusion: These findings provide an insight on the potential use of HIC, which remains the mainstay treatment for prostate cancer.

Download Full-text

Functional characterization of the three Drosophila retinal degeneration C (RDGC) protein phosphatase isoforms

PLoS ONE ◽

10.1371/journal.pone.0204933 ◽

2018 ◽

Vol 13 (9) ◽

pp. e0204933

Author(s):

Olaf Voolstra ◽

Lisa Strauch ◽

Matthias Mayer ◽

Armin Huber

Keyword(s):

Retinal Degeneration ◽

Protein Phosphatase ◽

Functional Characterization

Download Full-text

Functional Characterization of the Nep1-Like Protein Effectors of the Necrotrophic Pathogen – Alternaria brassicae

Frontiers in Microbiology ◽

10.3389/fmicb.2021.738617 ◽

2021 ◽

Vol 12 ◽

Author(s):

Deepak Duhan ◽

Shivani Gajbhiye ◽

Rajdeep Jaswal ◽

Ravindra Pal Singh ◽

Tilak Raj Sharma ◽

...

Keyword(s):

Cell Death ◽

Host Species ◽

Functional Characterization ◽

Subcellular Location ◽

Ethylene Biosynthesis ◽

Alternaria Brassicae ◽

Necrotrophic Pathogen ◽

Molecular Pattern ◽

Pathogen Associated Molecular Pattern

Alternaria brassicae is an important necrotrophic pathogen that infects the Brassicaceae family. A. brassicae, like other necrotrophs, also secretes various proteinaceous effectors and metabolites that cause cell death to establish itself in the host. However, there has been no systematic study of A. brassicae effectors and their roles in pathogenesis. The availability of the genome sequence of A. brassicae in public domain has enabled the search for effectors and their functional characterization. Nep1-like proteins (NLPs) are a superfamily of proteins that induce necrosis and ethylene biosynthesis. They have been reported from a variety of microbes including bacteria, fungi, and oomycetes. In this study, we identified two NLPs from A. brassicae viz. AbrNLP1 and AbrNLP2 and functionally characterized them. Although both AbrNLPs were found to be secretory in nature, they localized differentially inside the plant. AbrNLP2 was found to induce necrosis in both host and non-host species, while AbrNLP1 could not induce necrosis in both species. Additionally, AbrNLP2 was shown to induce pathogen-associated molecular pattern (PAMP)-triggered immunity in both host and non-host species. Overall, our study indicates that AbrNLPs are functionally and spatially (subcellular location) distinct and may play different but important roles during the pathogenesis of A. brassicae.

Download Full-text