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Proteomic analysis reveals a FANCA-modulated neddylation pathway involved in CXCR5 membrane targeting and cell

Xavier Renaudin1, Jean-Hugues Guervilly1, Said Aoufouchi2

  • 1Université Paris-Sud, 91400 Orsay, France CNRS UMR 8200 - Institut de Cancérologie Gustave Roussy, 94805 Villejuif, France Equipe Labellisée Ligue Contre le Cancer, 14 Rue Corvisart, 75013 Paris.

Journal of Cell Science
|July 13, 2014
PubMed

Insights

This study identifies new targets of the Fanconi anemia core (FANCcore) complex, revealing its role beyond DNA repair. Researchers found FANCA influences cell membrane protein neddylation, impacting cell motility.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Genetics

Background:

  • Fanconi anemia (FA) is a genetic disorder linked to bone marrow failure and cancer.
  • The FA core complex (FANCcore) is crucial for DNA repair via E3 ubiquitin-ligase activity.
  • FANCcore monoubiquitylates FANCD2 and FANCI during replicative stress.

Purpose of the Study:

  • To identify novel substrates of the FANCcore complex.
  • To investigate the role of FANCA and FANCC in post-translational modifications.
  • To explore the function of CXCR5 neddylation in cellular processes.

Main Methods:

  • Mass spectrometry was used to compare protein profiles in FANCcore-deficient and control cells.
  • Cells were treated with hydroxyurea to induce FANCD2 monoubiquitylation.
  • Specific protein modifications and cellular localization were analyzed.

Main Results:

  • FANCD2 and FANCI are the sole direct targets of the FANCcore complex.
  • Several proteins, primarily at the cell membrane, undergo FANCA/FANCC-dependent post-translational modification.
  • The chemokine receptor CXCR5 was found to be neddylated, a process modulated by FANCA.
  • CXCR5 neddylation targets it to the cell membrane and enhances cell migration and motility.

Conclusions:

  • The FANCcore complex has substrates beyond FANCD2 and FANCI.
  • FANCA plays a role in the neddylation pathway, affecting cell membrane protein localization.
  • A novel pathway involving FANCA, CXCR5 neddylation, and cell motility has been uncovered.
Keywords:
CXCR5Cell motilityFanconi anemiaLeukemiaNEDD8

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