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NONO ubiquitination is mediated by FBW7 and GSK3 β via a degron lost upon chromosomal rearrangement in cancer
Ist Teil von
Journal of cellular physiology, 2018-05, Vol.233 (5), p.4338-4344
Ort / Verlag
United States: Wiley Subscription Services, Inc
Erscheinungsjahr
2018
Link zum Volltext
Quelle
Wiley Online Library Journals Frontfile Complete
Beschreibungen/Notizen
NONO is an RNA‐binding protein involved in transcription, mRNA splicing, DNA repair, and checkpoint activation in response to UV radiation. NONO expression has been found altered in several tumor types, including prostate, colon, breast, melanoma, and in papillary renal carcinoma, in which an X chromosome inversion generates a NONO‐TFE3 fusion protein. Upon such rearrangement, NONO loses its C‐terminal domain. Through bioinformatics analysis, we identified a putative degron motif, known to be recognized by the Skp1‐Cul1‐F‐box‐protein (SCF) complex. Here, we evaluated how this domain could affect NONO protein biology. We showed that NONO interacts with the nuclear FBW7α isoform and its ubiquitination is regulated following modulation of the GSK3β kinase. Mutation of T428A/T432A within the degron impaired polyubiquitination upon FBW7α and GSK3β overexpression. Overall, our data suggest that NONO is likely subjected to proteasome‐mediated degradation and add NONO to the list of proteins targeted by FBW7, which is itself often deregulated in cancer.
NONO is an RNA‐binding protein involved in many cellular pathways. Its expression has been found altered in several tumor types and in papillary renal carcinoma, in which an X chromosome inversion generates a NONO‐TFE3 fusion protein. We identified a degron motif in NONO protein adding another protein to the long list of FBW7 targets.