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USP9X activates SMAD4. 13 / 13
3 | 9 1

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"During the development of PD, USP9X regulates the level of α-synuclein and activates SMAD4 by stabilizing it at K519 and subsequently promoting the TGF-β pathway (often correlated with several neurodegenerative diseases) ( xref )."

"Smad4 is monoubiquitinated in lysine 519 in vivo, a modification that inhibits smad4 by impeding association with phospho-smad2. Fam reverts this negative modification, re-empowering smad4 function;control of smad4 is a good way to regulate bone formation. Fam and ectodermin/tif1gamma (ecto) were reported to respectively regulate the de-ubiquitination and ubiquitination of smad4."

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"Sall4 shows an interaction with Usp9x (XREF_FIG B), an essential component of the TGF-beta and BMP signaling pathway, which activates Smad4 by removing a monoubiquitin group."

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"Loss of the USP9x homologue Fat facets in Drosophila inhibits the activity of the Smad4 homologue Medea through ubiquitination of Medea on K738 (equivalent to K519 in human Smad4) (Stinchfield et al.,[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

"Smad4 is monoubiquitinated in lysine 519 in vivo, a modification that inhibits smad4 by impeding association with phospho-smad2. Fam reverts this negative modification, re-empowering smad4 function;control of smad4 is a good way to regulate bone formation. Fam and ectodermin/tif1gamma (ecto) were reported to respectively regulate the de-ubiquitination and ubiquitination of smad4."

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"A recent study reported that USP9X activates SMAD4 by deubiquitination at K519, resulting in the activation of SMAD2/3, and promotion of TGFbeta pathway, which will induce cell apoptosis."

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"USP9x has been reported to increase SMAD4 activity by removing an inhibitory ubiquitin moiety [XREF_BIBR]."

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"USP9X was previously reported to regulate Smad4 transcriptional activity positively, thus we hypothesized that decreased USP9X expression would attenuate Smad4 function and TGF-beta responsiveness in HCC cell lines [XREF_BIBR]."

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"Removal of the mono-ubiquitin by the de-ubiquitinase FAM and USP9x restores Smad4 function [XREF_BIBR]."

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"Since USP9X was previously reported to positively regulate SMAD4 transcriptional activity 17 and SMAD4 is commonly mutated in PDA 4, we hypothesized that Usp9x loss would attenuate Smad4 function or TGFbeta responsiveness in PDA cell lines."

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"Thus, the de-ubiquitylase FAM and USP9 can remove K519 mono-ubiquitylation of Smad4 imposed by TIF1gamma, and thus restore Smad4 function."

"Smad4 is monoubiquitinated in lysine 519 in vivo, a modification that inhibits smad4 by impeding association with phospho-smad2. Fam reverts this negative modification, re-empowering smad4 function;control of smad4 is a good way to regulate bone formation. Fam and ectodermin/tif1gamma (ecto) were reported to respectively regulate the de-ubiquitination and ubiquitination of smad4."

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"3.5 USP9X targets SMAD4 for deubiquitylation in the TGFbeta pathway."