Homodimer of Two F-box Proteins βTrCP1 or βTrCP2 Binds to IκBα for Signal-dependent Ubiquitination*

By Hiroshi Suzuki, T. Chiba, Toshiaki Suzuki, T. Fujita, T. Ikenoue, M. Omata, K. Furuichi, H. Shikama, Keiji Tanaka. Journal of Biological Chemistry, 2000

142 citations recorded by the source corpus.

We found previously that overexpression of an F-box protein βTrCP1 and the structurally related βTrCP2 augments ubiquitination of phosphorylated IκBα (pIκBα) induced by tumor necrosis factor-α (TNF-α), but the relationship of the two homologous βTrCP proteins remains unknown. Herein we reveal that deletion mutants of βTrCP1 and βTrCP2 lacking the F-box domain suppressed ubiquitination and destruction of pIκBα as well as transcriptional activation of NF-κB. The ectopically expressed βTrCP1 and βTrCP2 formed both homodimer and heterodimer complexes without displaying the trimer complex. Dimerization of βTrCP1 and/or βTrCP2 takes place at their conserved NH2-terminal regions, termed a “D-domain” (for dimerization domain), located upstream of the F-box domain. The D-domain was necessary and sufficient for the dimer formation. Intriguingly, the βTrCP homodimer, but not the heterodimer, was selectively recruited to pIκBα induced by TNF-α. These results indicate that not only βTrCP1 but also βTrCP2 participates in the ubiquitination-dependent destruction of IκBα by forming SCFβTrCP1-βTrCP1 and SCFβTrCP2-βTrCP2 ubiquitin-ligase complexes.

Subfields: Cancer Research, Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/e4afe555c7e8761d3cc34550a46a718e03ea6633

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In Cancer Research

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Citations in the corpus

• Shared Pathways of IκB Kinase-Induced SCFβTrCP-Mediated Ubiquitination and Degradation for the NF-κB Precursor p105 and IκBα (2001, background): “bTrCP1 and bTrCP2 bind as homodimers to IkBa (48).”
• The Ubiquitin-Proteasome Pathway and Plant Development (2004, background): “There is evidence from yeast (Kominami et al., 1998), animals (Suzuki et al., 2000), and plants (Risseeuw et al., 2003) that some F-box proteins form heterodimers with other F-box proteins, which would lead to an even higher level of complexity.”