Fbx7 functions in the SCF complex regulating Cdk1-cyclin B-phosphorylated hepatoma up-regulated protein (HURP) proteolysis by a proline-rich region

Jung Mao Hsu, Yuan Chii G Lee, Chang Tze M Yu, Chi Ying F Huang

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Abstract

F-box proteins, components of SCF ubiquitin-ligase complexes, are believed to be responsible for substrate recognition and recruitment in SCF-mediated proteolysis. F-box proteins that have been identified to function in the SCF complexes to date mostly have substrate-binding motifs, such as WD repeats or leucine-rich repeats in their C termini. However, many F-box proteins lack recognizable substrate-binding modules; whether they can function in the SCF complexes remains unclear. We show here that Fbx7, an F-box protein without WD repeats and leucine-rich repeats, is required for the proteasome-mediated proteolysis of the hepatoma up-regulated protein (HURP). Depletion of Fbx7 by small interfering RNA leads to depression of HURP ubiquitination and accumulation of HURP abundance. In the SCFFbx7 complex, Fbx7 recruits HURP through its C-terminal proline-rich region in a Cdk1-cyclin B-phosphorylation dependent manner. Mutation of the multiple Cdk1-cyclin B phosphorylation sites on HURP or the proline-rich region of Fbx7 abolishes the association between Fbx7 and HURP. Thus, Fbx7 is a functional adaptor of the SCF complex with a proline-rich region as the substrate-binding module. In addition to Fbx7, data base analyses reveal two putative mammalian proline-rich region-containing F-box proteins, KIAA1783 and RIKEN cDNA 2410015K21. Taken together, these findings further expound the diverse substrate-recognition abilities of the SCF complexes.

Original languageEnglish
Pages (from-to)32592-32602
Number of pages11
JournalJournal of Biological Chemistry
Volume279
Issue number31
DOIs
Publication statusPublished - Jul 30 2004

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Proteolysis
Cyclin B
F-Box Proteins
Proline
Hepatocellular Carcinoma
Substrates
Phosphorylation
Proteins
Leucine
SKP Cullin F-Box Protein Ligases
Ubiquitination
Proteasome Endopeptidase Complex
Small Interfering RNA
Complementary DNA
Association reactions
Databases
Mutation

ASJC Scopus subject areas

  • Biochemistry

Cite this

Fbx7 functions in the SCF complex regulating Cdk1-cyclin B-phosphorylated hepatoma up-regulated protein (HURP) proteolysis by a proline-rich region. / Hsu, Jung Mao; Lee, Yuan Chii G; Yu, Chang Tze M; Huang, Chi Ying F.

In: Journal of Biological Chemistry, Vol. 279, No. 31, 30.07.2004, p. 32592-32602.

Research output: Contribution to journalArticle

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