Theileria annulata Hijacks Host Signaling: Integrated Phosphoproteomics and transcriptomics Unveils ERK1/2 as a Central Regulator of Host Transcription Factors.
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引用次数: 0
Abstract
THEILERIA: transformed bovine leukocytes exhibit cancer-like characteristics, but the molecular mechanisms driving these transformations remain unclear. This study provides the first comprehensive phosphoproteomic analysis of both host and parasite in Theileria annulata-infected leukocyte cell lines. We show that T. annulata significantly induces changes in the host protein phosphorylation, impacting key cancer-related processes such as apoptosis suppression, CAMK signaling, and telomere maintenance. A pivotal finding is the parasite's manipulation of the MAPK pathway via sustained ERK1/2 activation, which regulates the phosphorylation of critical transcription factors like RUNX3, FOSL2, BCL6, c-JUN, JUNB, and c-MYC. Transcriptomic analysis of genes controlled by these transcription factors confirmed their role in T. annulata replication. ERK inhibition disrupts phosphorylation, deactivates these transcription factors, and induces apoptosis in infected cells. This underscores the ERK-AP-1 axis as a central mechanism of Theileria pathogenesis and a promising therapeutic target. Additionally, parasite-specific phosphoproteins and kinases were identified, offering new insights into therapeutic strategies to combat infection.
期刊介绍:
The mission of MCP is to foster the development and applications of proteomics in both basic and translational research. MCP will publish manuscripts that report significant new biological or clinical discoveries underpinned by proteomic observations across all kingdoms of life. Manuscripts must define the biological roles played by the proteins investigated or their mechanisms of action.
The journal also emphasizes articles that describe innovative new computational methods and technological advancements that will enable future discoveries. Manuscripts describing such approaches do not have to include a solution to a biological problem, but must demonstrate that the technology works as described, is reproducible and is appropriate to uncover yet unknown protein/proteome function or properties using relevant model systems or publicly available data.
Scope:
-Fundamental studies in biology, including integrative "omics" studies, that provide mechanistic insights
-Novel experimental and computational technologies
-Proteogenomic data integration and analysis that enable greater understanding of physiology and disease processes
-Pathway and network analyses of signaling that focus on the roles of post-translational modifications
-Studies of proteome dynamics and quality controls, and their roles in disease
-Studies of evolutionary processes effecting proteome dynamics, quality and regulation
-Chemical proteomics, including mechanisms of drug action
-Proteomics of the immune system and antigen presentation/recognition
-Microbiome proteomics, host-microbe and host-pathogen interactions, and their roles in health and disease
-Clinical and translational studies of human diseases
-Metabolomics to understand functional connections between genes, proteins and phenotypes