F-box protein

Core components

F-box domain is a protein structural motif of about 50 amino acids that mediates protein–protein interactions. It has consensus sequence and varies in few positions. It was first identified in cyclin F. The F-box motif of Skp2, consisting of three alpha-helices, interacts directly with the SCF protein Skp1. F-box domains commonly exist in proteins in cancer with other protein–protein interaction motifs such as leucine-rich repeats (illustrated in the Figure) and WD repeats, which are thought to mediate interactions with SCF substrates.

Function

F-box proteins have also been associated with cellular functions such as signal transduction and regulation of the cell cycle. In plants, many F-box proteins are represented in gene networks broadly regulated by microRNA-mediated gene silencing via RNA interference. F-box proteins are involved in many plant vegetative and reproduction growth and development. For example, F-box protein-FOA1 involved in abscisic acid (ABA) signaling to affect the seed germination. ACRE189/ACIF1 can regulate cell death and defense when the pathogen is recognized in the Tobacco and Tomato plant.

In human cells, under high-iron conditions, two iron atoms stabilise the F-Box FBXL5 and then the complex mediates the ubiquitination of IRP2.

Regulation

F-box protein levels can be regulated by different mechanisms. The regulation can occur via protein degradation process and association with SCF complex . For example, in yeast, the F-box protein Met30 can be ubiquitinated in a cullin-dependent manner.

References

References

1. (November 2000). "Insights into SCF ubiquitin ligases from the structure of the Skp1-Skp2 complex". Nature.
2. (1996). "SKP1 connects cell cycle regulators to the ubiquitin proteolysis machinery through a novel motif, the F-box". Cell.
3. (2000). "The F-box protein family". Genome Biol..
4. (1999). "The F-box: a new motif for ubiquitin dependent proteolysis in cell cycle regulation and signal transduction". Prog. Biophys. Mol. Biol..
5. (2006). "MicroRNAS and their regulatory roles in plants". Annu Rev Plant Biol.
6. (2012). "Arabidopsis F-box gene FOA1 involved in ABA signaling". Science China Life Sciences.
7. (2008). "The F-box protein ACRE189/ACIF1 regulates cell death and defense responses activated during pathogen recognition in tobacco and tomato". Plant Cell.
8. (2011). "The FBXL5-IRP2 axis is integral to control of iron metabolism in vivo". Cell Metabolism.
9. (2006). "The yeast ubiquitin ligase SCFMet30: connecting environmental and intracellular conditions to cell division". Cell Division.