Alternative titles; symbols
HGNC Approved Gene Symbol: FBXO42
Cytogenetic location: 1p36.13 Genomic coordinates (GRCh38): 1:16,246,840-16,352,480 (from NCBI)
Members of the F-box protein family, such as FBXO42, are characterized by an approximately 40-amino acid F-box motif. SCF complexes, formed by SKP1 (SKP1A; 601434), cullin (see CUL1; 603134), and F-box proteins, act as protein-ubiquitin ligases. F-box proteins interact with SKP1 through the F box, and they interact with ubiquitination targets through other protein interaction domains (Jin et al., 2004).
By sequencing clones obtained from a size-fractionated fetal brain cDNA library, Nagase et al. (2000) cloned FBXO42, which they designated KIAA1332. The deduced protein contains at least 651 amino acids. RT-PCR ELISA detected intermediate expression in adult brain, testis, ovary, liver, and kidney, low expression in heart and fetal brain, and little to no expression in all other tissues examined. Low to intermediate expression was detected in all specific brain regions examined, with highest expression in amygdala and caudate nucleus.
Jin et al. (2004) reported that the FBXO42 protein contains an F box in its N terminus and 3 central kelch repeats.
By RT-PCR of a mammary library, Sun et al. (2009) cloned full-length FBXO42, which they called JFK. The deduced 717-amino acid protein has a calculated molecular mass of approximately 77 kD. JFK contains an N-terminal F-box motif followed by a kelch domain. Northern blot analysis detected variable expression of a 3-kb JFK transcript. Expression was highest in heart and skeletal muscle, moderate in placenta, liver, and pancreas, and low in brain, lung, and kidney. Western blot analysis of human U2OS cells detected endogenous JFK at an apparent molecular mass of 77 kD.
By immunoprecipitation analysis of U2OS cells, Sun et al. (2009) detected JFK in an SCF complex containing CUL1, SKP1, and RBX1 (603814), but not CUL3 (603136). Mutation analysis revealed that the F-box of JFK was required for its direct interaction with SKP1. Mass spectrometric analysis also revealed the presence of p53 (TP53; 191170) in the SCF immunocomplex. Protein pull-down and mutation analyses confirmed a direct interaction between the kelch domain of JFK and p53. Overexpression of JFK increased ubiquitination and degradation of p53, and these effects were blocked by a proteasome inhibitor. Overexpression and knockdown studies showed that JFK-mediated degradation of p53 reduced 53-mediated transactivation activity and transcription of p53-dependent genes and countered p53-mediated apoptosis, growth suppression, and checkpoint control. Sun et al. (2009) concluded that JFK is a critical negative regulator of p53.
Jin et al. (2004) stated that the FBXO42 gene maps to chromosome 1p36.23-p36.11 and the mouse Fbxo42 gene maps to chromosome 4D3.
Jin, J., Cardozo, T., Lovering, R. C., Elledge, S. J., Pagano, M., Harper, J. W. Systematic analysis and nomenclature of mammalian F-box proteins. Genes Dev. 18: 2573-2580, 2004. [PubMed: 15520277] [Full Text: https://doi.org/10.1101/gad.1255304]
Nagase, T., Kikuno, R., Ishikawa, K., Hirosawa, M., Ohara, O. Prediction of the coding sequences of unidentified human genes. XVI. The complete sequences of 150 new cDNA clones from brain which code for large proteins in vitro. DNA Res. 7: 65-73, 2000. [PubMed: 10718198] [Full Text: https://doi.org/10.1093/dnares/7.1.65]
Sun, L., Shi, L., Li, W., Yu, W., Liang, J., Zhang, H., Yang, X., Wang, Y., Li, R., Yao, X., Yi, X., Shang, Y. JFK, a Kelch domain-containing F-box protein, links the SCF complex to p53 regulation. Proc. Nat. Acad. Sci. 106: 10195-10200, 2009. [PubMed: 19509332] [Full Text: https://doi.org/10.1073/pnas.0901864106]