Proteasomal degradation of the multifunctional regulator YB-1 is mediated by an F-Box protein induced during programmed cell death

FEBS Lett. 2006 Jul 10;580(16):3921-30. doi: 10.1016/j.febslet.2006.06.023. Epub 2006 Jun 21.

Abstract

F-Box proteins (FBPs) are variable adaptor proteins that earmark protein substrates for ubiquination and destruction by the proteasome. Through their N-terminal F-box motif, they couple specific protein substrates to a catalytic machinery known as SCF (Skp-1/Cul1/F-Box) E3-ubiquitin ligase. Typical FBPs bind the specific substrates in a phosphorylation dependent manner via their C-termini using either leucine rich repeats (LRR) or tryptophan-aspartic acid (WD40) domains for substrate recognition. By using a gene trap strategy that selects for genes induced during programmed cell death, we have isolated the mouse homolog of the hypothetical human F-Box protein 33 (FBX33). Here we identify FBX33 as a component of an SCF E3-ubiquitin ligase that targets the multifunctional regulator Y-box binding protein 1 (YB-1)/dbpB/p50 for polyubiquitination and destruction by the proteasome. By targeting YB-1 for proteasomal degradation, FBX33 negatively interferes with YB-1 mediated functions. In contrast to typical FBPs, FBX33 has no C-terminal LRR or WD40 domains and associates with YB-1 via its N-terminus. The present study confirms the existence of a formerly hypothetical F-Box protein in living cells and describes one of its substrates.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Apoptosis*
  • COS Cells
  • Cells, Cultured
  • Chlorocebus aethiops
  • Humans
  • Mice
  • Molecular Sequence Data
  • Nerve Tissue Proteins / chemistry
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Polyubiquitin / metabolism
  • Proteasome Endopeptidase Complex / metabolism*
  • Protein Binding
  • Protein Processing, Post-Translational*
  • Protein Structure, Tertiary
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • SKP Cullin F-Box Protein Ligases / metabolism
  • Transcription Factors / chemistry
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcriptional Activation / genetics
  • Y-Box-Binding Protein 1 / metabolism*

Substances

  • Fbxo33 protein, mouse
  • Nerve Tissue Proteins
  • RNA, Messenger
  • Transcription Factors
  • Y-Box-Binding Protein 1
  • Polyubiquitin
  • SKP Cullin F-Box Protein Ligases
  • Proteasome Endopeptidase Complex