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Linking Ubiquitin Signaling To Fragile X Syndrome (Fxs)

Reference : PhD Izabela Sumara

Publication de l'offre : 26 janvier 2018

Fragile X syndrome (FXS) is the most common form of cognitive human disability, for which no efficient therapy exists to date. It is caused by silencing of Fragile X mental retardation protein FMRP, which belongs to the Fragile X-related (FXR) protein family together with FXR1 and FXR2. These proteins are RNA binding proteins that critically control translational processes of hundreds of transcripts. However, their roles beyond RNA regulation remain elusive.


We found an unexpected link between FXR proteins and nuclear organization and showed that they regulate assembly of nucleoporins (NUPs) at the nuclear envelope (NE). We further identified the ubiquitin binding protein NICE-4 as a specific partner of FXR proteins that controls their localization to NE. Thus, we have identified the first regulatory factor of the FXR-NUP pathway that links it to ubiquitin signaling. We hypothesize that its misregulation will change differentiation programs and contribute to the pathology of FXS and related human disorders.


The aim of this project is to characterize the role of ubiquitin signaling in Fragile X syndrome and related diseases.

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