Functional Crosstalk of the Pseudophosphatase STYX with F-box proteins

• Applicant: Privatdozent Dr. Gunter Schmidtke, since 8/2016
• Subject Area: Cell Biology ; Biochemistry
• Term: from 2015 to 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 271101596

Pseudophosphatase remain poorly understood with respect to their roles in biology and disease. We recently showed that the pseudophosphatase STYX regulates signaling by mitogen activated protein kinases. However, since STYX is catalytically inactive we hypothesized that this pseudophosphatase might have evolved to regulate other family proteins beyond kinases. By mapping the interactome of STYX we found that it interacts with several F-box proteins (FBPs) that belong to the Cullin-RING ligases of ubiquitin transfer proteins that regulate the turnover of a fifth of the mammalian proteome. One of the FBPs is a protein called FBXW7, a well-known tumor-suppressor protein mutated in 9% of all human cancers. Our goals are:(i) characterization the binary interaction of STYX and FBPs with respect to the domains involved in their interaction. (ii) Investigate whether STYX is a substrate for any of the FBPs(iii) Explore the STYX-FBXW7 connection in the context of cancer. Beside cellular assays for effects of STYX and FBXW7 on proliferation and apoptosis, we will analyze a large cohort of patients to determine effects of differential STYX/FBXW7 expressions of prognosis of breast cancer patients. Overall, our study will lead to a better understanding of the role of the pseudophosphatase STYX in cell biology. Moreover, our results from cancer patients could lead to the establishment of STYX as a new therapeutic target or as a prognostic marker.

• DFG Programme: Research Grants
• Ehemaliger Antragsteller: Professor Dr. Hesso Farhan, until 7/2016