Proteasomal degradation of the multifunctional regulator YB-1 is mediated by an F-Box protein induced during programmed cell death |
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Authors: | Lutz Marcus Wempe Frank Bahr Inke Zopf Dieter von Melchner Harald |
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Affiliation: | Department for Molecular Hematology, University of Frankfurt Medical School, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany. |
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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. |
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Keywords: | AIG30-12-1, apoptosis-induced gene 30-12-1 CSD, cold shock domain Cul1, Cullin 1 FBPs, F-Box proteins FBX33, F-box protein 33 GST, glutathione S-transferase HA, haemagglutinin IL-2, interleukin-2 IL-3, interleukin-3 IRE, iron responsive element IRP2, IRE binding protein 2 LRR, leucin rich repeats mdr-1, multidrug resistance protein 1 MHC-II, major histocompatibility complex class II PCD, programmed cell death SCF, Skp-1/Cul1/F-box complex SKP1, S-phase kinase-associated protein 1 WD40, tryptophan-aspartic acid domains YB-1, Y-box binding protein 1 |
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