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Fbxo45 forms a novel ubiquitin ligase complex and is required for neuronal development.

Fbxo45 is an F-box protein that is restricted to the nervous system. Unlike other F-box proteins, Fbxo45 was found not to form an SCF complex as a result of an amino acid substitution in the consensus sequence for Cul1 binding. Proteomics analysis revealed that Fbxo45 specifically associates with PAM (protein associated with Myc), a RING finger-type ubiquitin ligase. Mice deficient in Fbxo45 were generated and found to die soon after birth as a result of respiratory distress. Fbxo45(-)(/)(-) embryos show abnormal innervation of the diaphragm, impaired synapse formation at neuromuscular junctions, and aberrant development of axon fiber tracts in the brain. Similar defects are also observed in mice lacking Phr1 (mouse ortholog of PAM), suggesting that Fbxo45 and Phr1 function in the same pathway. In addition, neuronal migration was impaired in Fbxo45(-)(/)(-) mice. These results suggest that Fbxo45 forms a novel Fbxo45-PAM ubiquitin ligase complex that plays an important role in neural development.

Pubmed ID: 19398581


  • Saiga T
  • Fukuda T
  • Matsumoto M
  • Tada H
  • Okano HJ
  • Okano H
  • Nakayama KI


Molecular and cellular biology

Publication Data

July 16, 2009

Associated Grants


Mesh Terms

  • Amino Acid Sequence
  • Animals
  • Body Patterning
  • Brain
  • Carrier Proteins
  • Cell Line
  • Cell Movement
  • F-Box Proteins
  • Genotype
  • Humans
  • Mice
  • Mice, Knockout
  • Molecular Sequence Data
  • Multiprotein Complexes
  • Neural Pathways
  • Neurogenesis
  • Neuromuscular Junction
  • Neurons
  • Protein Binding
  • Sequence Homology, Amino Acid
  • Spinal Cord
  • Ubiquitin-Protein Ligases