NONO ubiquitination is mediated by FBW7 and GSK3 ß via a degron lost upon chromosomal rearrangement in cancer.
J Cell Physiol
; 233(5): 4338-4344, 2018 05.
Article
em En
| MEDLINE
| ID: mdl-29150959
ABSTRACT
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 GSK3ß kinase. Mutation of T428A/T432A within the degron impaired polyubiquitination upon FBW7α and GSK3ß 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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Ligação a RNA
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Proteínas Associadas à Matriz Nuclear
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Fatores de Transcrição de Octâmero
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Glicogênio Sintase Quinase 3 beta
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Proteína 7 com Repetições F-Box-WD
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Neoplasias
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article