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Radaszkiewicz, K. A.

Publications and source records attributed to Radaszkiewicz, K. A..

2 recordsLinked to original sources

Dual Specificity Phosphatase 7 Drives the Formation of Cardiac Mesoderm in Mouse Embryonic Stem Cells

Dual specificity phosphatase 7 (DUSP7) is a protein belonging to a broad group of phosphatases that 14 can dephosphorylate phosphoserine/phosphothreonine as well as phosphotyrosine residues within the 15 same substrate. DUSP7 has been linked to the negative regulation of mitogen activated protein kinases 16 (MAPK), and in particular to the regulation of extracellular signal-regulated kinases 1 and 2 (ERK1/2). 17 MAPKs play an important role in embryonic development, where their duration, magnitude, and 18 spatiotemporal activity must be strictly controlled by other proteins, among others by DUSPs. In this 19 study, we focused on the effect of DUSP7 depletion on the in vitro differentiation of mouse embryonic 20 stem (ES) cells. We showed that even though DUSP7 knock-out ES cells do retain some of their basic 21 characteristics, when it comes to differentiation, they preferentially differentiate towards neural cells, 22 while the formation of early cardiac mesoderm is repressed. Therefore, our data indicate that DUSP7 23 is necessary for the correct formation of neuroectoderm and cardiac mesoderm during the in vitro 24 differentiation of ES cells.

cell biology↗

RNF43 inhibits WNT5A driven signaling and suppresses melanoma invasion

RNF43 is a E3 ubiquitin ligase and known negative regulator of WNT/{beta}-catenin signaling. We demonstrate that RNF43 is also regulator of noncanonical WNT5A-induced signaling in human cells. Analysis of the RNF43 interactome using BioID and immunoprecipitation showed that RNF43 can interact with the core receptor complex components dedicated to the noncanonical Wnt pathway such as ROR1, ROR2, VANGL1 and VANGL2. RNF43 triggers VANGL2 ubiquitination and proteasomal degradation and clathrin-dependent internalization of ROR1 receptor. This activity of RNF43 is physiologically relevant and blocks pro-metastatic WNT5A signaling in melanoma. RNF43 inhibits responses to WNT5A, which results in the suppression of invasive properties of melanoma cells. Furthermore, RNF43 prevented WNT5A-assisted development of resistance to BRAF V600E inhibitor. In line with these findings, RNF43 expression decreases during melanoma progression and RNF43-low patients have worse prognosis. We conclude that RNF43 is a newly discovered negative regulator of WNT5A-mediated biological responses that desensitizes cells to WNT5A.

cancer biology↗