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RSS FeedsIJMS, Vol. 23, Pages 11588: A Degradation Motif in STAU1 Defines a Novel Family of Proteins Involved in Inflammation (International Journal of Molecular Sciences)

 
 

30 september 2022 15:48:38

 
IJMS, Vol. 23, Pages 11588: A Degradation Motif in STAU1 Defines a Novel Family of Proteins Involved in Inflammation (International Journal of Molecular Sciences)
 


Cancer development is regulated by inflammation. Staufen1 (STAU1) is an RNA-binding protein whose expression level is critical in cancer cells as it is related to cell proliferation or cell death. STAU1 protein levels are downregulated during mitosis due to its degradation by the E3 ubiquitin ligase anaphase-promoting complex/cyclosome (APC/C). In this paper, we map the molecular determinant involved in STAU1 degradation to amino acids 38–50, and by alanine scanning, we shorten the motif to F39PxPxxLxxxxL50 (FPL-motif). Mutation of the FPL-motif prevents STAU1 degradation by APC/C. Interestingly, a search in databases reveals that the FPL-motif is shared by 15 additional proteins, most of them being involved in inflammation. We show that one of these proteins, MAP4K1, is indeed degraded via the FPL-motif; however, it is not a target of APC/C. Using proximity labeling with STAU1, we identify TRIM25, an E3 ubiquitin ligase involved in the innate immune response and interferon production, as responsible for STAU1 and MAP4K1 degradation, dependent on the FPL-motif. These results are consistent with previous studies that linked STAU1 to cancer-induced inflammation and identified a novel degradation motif that likely coordinates a novel family of proteins involved in inflammation. Data are available via ProteomeXchange with the identifier PXD036675.


 
59 viewsCategory: Biochemistry, Biophysics, Molecular Biology
 
IJMS, Vol. 23, Pages 11587: Study on βTCP/P(3HB) Scaffolds—Physicochemical Properties and Biological Performance in Low Oxygen Concentration (International Journal of Molecular Sciences)
IJMS, Vol. 23, Pages 11590: Prognostic and Immunological Role of STK38 across Cancers: Friend or Foe? (International Journal of Molecular Sciences)
 
 
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