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   Computational models of melanoma.; ; et al in Theoretical biology & medical modelling (2020), 17(1), 8 Genes, proteins, or cells influence each other and consequently create patterns, which can be increasingly better observed by experimental biology and medicine. Thereby, descriptive methods of statistics ... [more ▼] Genes, proteins, or cells influence each other and consequently create patterns, which can be increasingly better observed by experimental biology and medicine. Thereby, descriptive methods of statistics and bioinformatics sharpen and structure our perception. However, additionally considering the interconnectivity between biological elements promises a deeper and more coherent understanding of melanoma. For instance, integrative network-based tools and well-grounded inductive in silico research reveal disease mechanisms, stratify patients, and support treatment individualization. This review gives an overview of different modeling techniques beyond statistics, shows how different strategies align with the respective medical biology, and identifies possible areas of new computational melanoma research. [less ▲] Detailed reference viewed: 98 (4 UL) Cancer Cells Employ Nuclear Caspase-8 to Overcome the p53-Dependent G2/M Checkpoint through Cleavage of USP28.; ; et al in Molecular cell (2020) Cytosolic caspase-8 is a mediator of death receptor signaling. While caspase-8 expression is lost in some tumors, it is increased in others, indicating a conditional pro-survival function of caspase-8 in ... [more ▼] Cytosolic caspase-8 is a mediator of death receptor signaling. While caspase-8 expression is lost in some tumors, it is increased in others, indicating a conditional pro-survival function of caspase-8 in cancer. Here, we show that tumor cells employ DNA-damage-induced nuclear caspase-8 to override the p53-dependent G2/M cell-cycle checkpoint. Caspase-8 is upregulated and localized to the nucleus in multiple human cancers, correlating with treatment resistance and poor clinical outcome. Depletion of caspase-8 causes G2/M arrest, stabilization of p53, and induction of p53-dependent intrinsic apoptosis in tumor cells. In the nucleus, caspase-8 cleaves and inactivates the ubiquitin-specific peptidase 28 (USP28), preventing USP28 from de-ubiquitinating and stabilizing wild-type p53. This results in de facto p53 protein loss, switching cell fate from apoptosis toward mitosis. In summary, our work identifies a non-canonical role of caspase-8 exploited by cancer cells to override the p53-dependent G2/M cell-cycle checkpoint. [less ▲] Detailed reference viewed: 39 (2 UL)Impaired serine metabolism complements LRRK2-G2019S pathogenicity in PD patientsNickels, Sarah  ; ; Bolognin, Silvia et alin Parkinsonism and Related Disorders (2019) Detailed reference viewed: 184 (27 UL) |
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