AI Article Synopsis
- Recent research found that caspase-3 cleaves Par-4, leading to a 25kDa fragment (cl-Par-4) that accumulates significantly in certain cancer cell types under stress.
- Upon treatment with the chemotherapy drug cisplatin, cl-Par-4 levels surged up to 50 times, suggesting that cisplatin may protect this fragment from being broken down by the proteasome.
- Pathway analyses indicated that the PI3K pathway promotes cl-Par-4 accumulation, while the MAPK pathway reduces it, urging the need for more studies to understand the role of Par-4 in gynecological cancers.
Article Abstract
We recently reported the caspase3-dependent cleavage of Par-4 resulting in the accumulation of a 25kDa cleaved-Par-4 (cl-Par-4) fragment and we investigated in the present study the mechanisms regulating this fragment using cl-Par-4-expressing stable clones derived from ovarian and endometrial cancer cell lines.Cl-Par-4 protein was weakly express in all stable clones despite constitutive expression. However, upon cisplatin treatment, cl-Par-4 levels increased up to 50-fold relative to baseline conditions. Treatment of stable clones with proteasome and translation inhibitors revealed that cisplatin exposure might in fact protect cl-Par-4 from proteasome-dependent degradation. PI3K and MAPK pathways were also implicated as evidenced by an increase of cl-Par-4 in the presence of PI3K inhibitors and a decrease using MAPK inhibitors. Finally using bioinformatics resources, we found diverse datasets showing similar results to those we observed with the proteasome and cl-Par-4 further supporting our data.These new findings add to the complex mechanisms regulating Par-4 expression and activity, and justify further studies addressing the biological significance of this phenomenon in gynaecological cancer cells.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5095052 | PMC |
| http://dx.doi.org/10.18632/oncotarget.9235 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Characterization of a Major Quantitative Trait Locus for the Whiteness of Rice Grain Using Chromosome Segment Substitution Lines.
Plants (Basel)
December 2024
Key Laboratory of Plant Functional Genomics of the Ministry of Education/Zhongshan Biological Breeding Laboratory, Yangzhou University, Yangzhou 225009, China.
The whiteness of rice grains (WRG) is a key indicator of appearance quality, directly impacting its commercial value. The trait is quantitative, influenced by multiple factors, and no specific genes have been cloned to date. In this study, we first examined the correlation between the whiteness of polished rice, cooked rice, and rice flour, finding that the whiteness of rice flour significantly correlated with both polished and cooked rice.
View Article and Find Full Text PDFEvolution of community-associated MRSA: a 20-year genomic and epidemiological study in Region Örebro County, Sweden.
Front Microbiol
December 2024
Department of Laboratory Medicine, Clinical Microbiology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
Background: Methicillin-resistant (MRSA) has been an issue in healthcare since the 1960s. It was initially found only in healthcare facilities, but in the late 1990s it began to be seen with no healthcare connexion. The mechanisms of intercontinental and national spread are not fully understood, as sometimes novel outbreaks occur without any identifiable source or connexion to locally dominant clonal clusters.
View Article and Find Full Text PDFCoronavirus disease 2019 (COVID-19), caused by infection with the enveloped RNA betacoronavirus, SARS-CoV-2, led to a global pandemic involving over 7 million deaths. Macrophage inflammatory responses impact COVID-19 severity; however, it is unclear whether macrophages are infected by SARS-CoV-2. We sought to identify mechanisms regulating macrophage expression of ACE2, the primary receptor for SARS-CoV-2, and to determine if macrophages are susceptible to productive infection.
View Article and Find Full Text PDFA point mutation in the pepper veinal mottle virus 6K1 protein yields a stable attenuated strain for engineering virus resistance in pepper plants.
Plant Dis
January 2025
No. 58, Renmin AvenueHaikou, China, 570228;
A total of 164 viruses have been identified in peppers worldwide. To combat viruses, pathogen-derived resistance (PDR) has been employed by expressing a viral genomic segment or a viral protein in host plants. Unfortunately, peppers are recalcitrant to genetic transformation and regeneration.
View Article and Find Full Text PDFSingle-Cell Lineage Tracing and Clonal State-Fate Analysis.
Methods Mol Biol
January 2025
Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Catalonia, Spain.
Lineage tracing has significantly advanced our comprehension in many areas of biology, such as development or immunity, by precisely measuring cellular processes like migration, division, or differentiation across labeled cells and their progeny. Traditional recombinase-based prospective lineage tracing is limited by the need for a priori cell type information and is constrained in the numbers of clones it can simultaneously track. In this sense, clonal lineage tracing with integrated random barcodes offers a robust alternative, enabling researchers to label and track a vast array of cells and their progeny over time.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!