Francis Brühlmann (Bern / CH), Carmen Perry (Bern / CH), Charlotte Griessen (Bern / CH), Dr. Arunasalam Naguleswaran (Bern / CH), Dr. Kerry Woods (Bern / CH), Prof. Philipp Olias (Bern / CH; Gießen / DE)
Abstract text
Theileria annulata is a tick-transmitted apicomplexan parasite that causes a fatal cancer-like disease in the bovine host. The transient malignant phenotype is not based on genome instability or mutations at the DNA level as in cancer cells. We hypothesized that exported parasite proteins are responsible for the observed alteration of host signaling pathways in infected leukocytes. Only few exported proteins have been identified so far. To reveal uncharacterized Theileria effector proteins we used the TurboID proximity labeling technology and targeted the host cell nucleus and parasite membrane. By this approach we identified a novel repetitive protein locus of four intrinsically disordered proteins uniquely present in transformative T. annulata and absent in the non-transformative species T. orientalis. Co-immunoprecipitation experiments revealed an interaction of the exported protein NIDP2 with the host proteins NOC2L and STAG2. NOC2L is a protein involved in tumor suppressor p53 silencing. The STAG2 gene, another known tumor suppressor, encodes a subunit of the cohesin complex, which is involved in sister chromatid cohesion, with important roles in chromatin structure maintenance, gene expression and DNA repair. Further investigations are now being undertaken to analyze the contribution of these interactions to host cell transformation. The latest results will be presented at the conference.
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