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Proteasomal degradation of the multifunctional regulator YB‐1 is mediated by an F‐Box protein induced during programmed cell death
Author(s) -
Lutz Marcus,
Wempe Frank,
Bahr Inke,
Zopf Dieter,
von Melchner Harald
Publication year - 2006
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2006.06.023
Subject(s) - regulator , programmed cell death , microbiology and biotechnology , degradation (telecommunications) , chemistry , apoptosis , cell , biophysics , biology , biochemistry , engineering , electronic engineering , gene
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.