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A new subfamily of structurally related human F-box proteins
Gennady P Ilyin1, Anne-Laure Sérandour, Christelle Pigeon
1INSERM U522, Hôpital Pontchaillou, Avenue de la Bataille Flandre-Dunkerque, 35033 Rennes, France. Guennadi.Iline@rennes.inserm.fr
Abstract:
F-box proteins, a critical component of the evolutionary conserved ubiquitin-protein ligase complex SCF (Skp1/Cdc53-Cullin1/F-box), recruit substrates for ubiquitination and consequent degradation through their specific protein-protein interaction domains. Here, we report the identification of full-length cDNAs encoding three novel human F-box proteins named FBG3, FBG4 and FBG5 which display similarity with previously identified NFB42 (FBX2) and FBG2 (FBX6) proteins. All five proteins are characterized by an approximately 180-amino-acid (aa) conserved C-terminal domain and thus constitute a third subfamily of mammalian F-box proteins. Analysis of genomic organization of the five FBG genes revealed that all of them consist of six exons and five introns. FBG1, FBG2 and FBG3 genes are located in tandem on chromosome 1p36, and FBG4 and FBG5 are mapped to chromosome 19q13. FBG genes are expressed in a limited number of human tissues including kidney, liver, brain and muscle tissues. Expression of rat FBG2 gene was found related to differentiation/proliferation status of hepatocytes. Specifically, FBG2 mRNA was expressed in foetal liver, decreased after birth and re-accumulated in adult liver. Expression of FBG2 was strongly inhibited in hepatoma cells by okadaic acid.
Insights
We identified three new human F-box proteins (FBG3, FBG4, FBG5), forming a new subfamily. These F-box proteins are involved in the SCF ubiquitin ligase complex and show tissue-specific expression patterns.
Area of Science:
- Molecular Biology
- Genetics
- Cell Biology
Background:
- F-box proteins are key components of the SCF (Skp1/Cdc53-Cullin1/F-box) ubiquitin ligase complex.
- They play a crucial role in substrate recruitment for ubiquitination and degradation.
- This study focuses on a novel subfamily of mammalian F-box proteins.
Purpose of the Study:
- To identify and characterize novel human F-box proteins.
- To investigate the genomic organization and expression patterns of these newly identified F-box proteins.
- To explore the potential role of FBG2 in liver cell differentiation and proliferation.
Main Methods:
- Identification of full-length cDNAs for three novel human F-box proteins (FBG3, FBG4, FBG5).
- Comparative analysis of protein sequences to identify conserved domains.
- Analysis of genomic organization, including exon-intron structure and gene mapping.
- Tissue expression profiling using Northern blot or similar techniques.
- Investigation of rat FBG2 expression in relation to hepatocyte differentiation and proliferation.
Main Results:
- Three novel human F-box proteins, FBG3, FBG4, and FBG5, were identified.
- These proteins, along with NFB42 (FBX2) and FBG2 (FBX6), form a new subfamily characterized by a conserved C-terminal domain.
- All five FBG genes share a six-exon, five-intron structure.
- FBG1, FBG2, and FBG3 genes are located in tandem on chromosome 1p36; FBG4 and FBG5 are on chromosome 19q13.
- FBG genes are expressed in limited human tissues: kidney, liver, brain, and muscle.
- Rat FBG2 expression is linked to hepatocyte differentiation, with distinct patterns in fetal, neonatal, and adult liver.
- Okadaic acid treatment inhibited FBG2 expression in hepatoma cells.
Conclusions:
- The identification of FBG3, FBG4, and FBG5 expands the known diversity of mammalian F-box proteins.
- The conserved domain and genomic structure suggest a functional relationship within this new subfamily.
- Tissue-specific expression patterns indicate specialized roles for these F-box proteins.
- FBG2's expression profile suggests a role in liver development and potentially in hepatocellular carcinoma.