Structure and expression of the gene encoding mouse F-box protein, Fwd2

Masatoku Miura, Shigetsugu Hatakeyama, Kimihiko Hattori, Kei Ichi Nakayama

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

A novel class of ubiquitin ligases, termed the SCF complex, consists of invariable components, Skp1 and Cullin, and variable components called F-box proteins, which have a primary role in determining substrate specificity. We have isolated a cDNA encoding the mouse F-box protein Fwd2 (also known as MD6) as a possible constituent of an SCF-type ubiquitin ligase. Fwd2 cDNA contains 1890 bp with a 1362-bp open reading frame and encodes an approximately 51.5-kDa protein. Fwd2 is expressed predominantly in liver and, to a lesser extent, in the testis, lung, heart, and skeletal muscle. Immunofluorescence staining for Fwd2 protein shows a pattern with the cytoplasm. A coimmunoprecipitation assay has revealed the in vivo interaction between Skp1 and Fwd2 through the F-box domain. Fwd2 also interacts with Cul1 through Skp1, suggesting that Skp1, Cul1, and the F-box protein Fwd2 form an SCF complex (SCF(Fwd2)). We have also isolated and determined the nucleotide sequence and genomic organization of the gene that encodes mouse Fwd2. This gene spans approximately 17 kb and consists of six exons and five introns. Our results suggest that Fwd2 is an F-box protein that constitutes an SCF ubiquitin ligase complex and that it plays a critical role in the ubiquitin- dependent degradation of proteins expressed in the liver.

Original languageEnglish
Pages (from-to)50-58
Number of pages9
JournalGenomics
Volume62
Issue number1
DOIs
Publication statusPublished - Nov 15 1999

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SKP Cullin F-Box Protein Ligases
F-Box Proteins
Gene Expression
Complementary DNA
Cullin Proteins
Liver
Ubiquitin
Substrate Specificity
Introns
Open Reading Frames
Proteolysis
Genes
Fluorescent Antibody Technique
Testis
Exons
Myocardium
Cytoplasm
Skeletal Muscle
Proteins
Staining and Labeling

All Science Journal Classification (ASJC) codes

  • Genetics

Cite this

Structure and expression of the gene encoding mouse F-box protein, Fwd2. / Miura, Masatoku; Hatakeyama, Shigetsugu; Hattori, Kimihiko; Nakayama, Kei Ichi.

In: Genomics, Vol. 62, No. 1, 15.11.1999, p. 50-58.

Research output: Contribution to journalArticle

Miura, Masatoku ; Hatakeyama, Shigetsugu ; Hattori, Kimihiko ; Nakayama, Kei Ichi. / Structure and expression of the gene encoding mouse F-box protein, Fwd2. In: Genomics. 1999 ; Vol. 62, No. 1. pp. 50-58.
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