F-box proteins are proteins containing at least one F-box domain. The first identified F-box protein is one of three components of the

SCF complex Skp, Cullin, F-box containing complex (or SCF complex) is a multi-protein E3 ubiquitin ligase complex that catalyzes the ubiquitination of proteins destined for 26S proteasomal degradation. Along with the anaphase-promoting complex, SCF has impo ...

, which mediates

ubiquitin Ubiquitin is a small (8.6 kDa) regulatory protein found in most tissues of eukaryotic organisms, i.e., it is found ''ubiquitously''. It was discovered in 1975 by Gideon Goldstein and further characterized throughout the late 1970s and 1980s. Fou ...

ation of proteins targeted for degradation by the 26S

proteasome Proteasomes are protein complexes which degrade unneeded or damaged proteins by proteolysis, a chemical reaction that breaks peptide bonds. Enzymes that help such reactions are called proteases. Proteasomes are part of a major mechanism by wh ...

Core components

F-box domain is a protein

structural motif In a chain-like biological molecule, such as a protein or nucleic acid, a structural motif is a common three-dimensional structure that appears in a variety of different, evolutionarily unrelated molecules. A structural motif does not have ...

of about 50

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...

s that mediates

protein–protein interaction Protein–protein interactions (PPIs) are physical contacts of high specificity established between two or more protein molecules as a result of biochemical events steered by interactions that include electrostatic forces, hydrogen bonding and ...

s. 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 S-phase kinase-associated protein 1 is an enzyme that in humans is encoded by the ''SKP1'' gene. This gene encodes a protein that is a member of the SCF ubiquitin ligase protein complex. It binds to F-box proteins (proteins containing an F- ...

. F-box domains commonly exist in proteins in cancer with other protein–protein interaction motifs such as

leucine-rich repeat A leucine-rich repeat (LRR) is a protein structural motif that forms an α/β horseshoe fold. It is composed of repeating 20–30 amino acid stretches that are unusually rich in the hydrophobic amino acid leucine. These tandem repeats commo ...

s (illustrated in the Figure) and

WD repeat The WD40 repeat (also known as the WD or beta-transducin repeat) is a short structural motif of approximately 40 amino acids, often terminating in a tryptophan-aspartic acid (W-D) dipeptide. Tandem copies of these repeats typically fold togethe ...

s, which are thought to mediate interactions with SCF substrates.

Function

F-box proteins have also been associated with cellular functions such as

signal transduction Signal transduction is the process by which a chemical or physical signal is transmitted through a cell as a series of molecular events, most commonly protein phosphorylation catalyzed by protein kinases, which ultimately results in a cellular ...

and regulation of the

cell cycle The cell cycle, or cell-division cycle, is the series of events that take place in a cell that cause it to divide into two daughter cells. These events include the duplication of its DNA (DNA replication) and some of its organelles, and subs ...

. In plants, many F-box proteins are represented in

gene network A gene (or genetic) regulatory network (GRN) is a collection of molecular regulators that interact with each other and with other substances in the cell to govern the gene expression levels of mRNA and proteins which, in turn, determine the fun ...

s broadly regulated by

microRNA MicroRNA (miRNA) are small, single-stranded, non-coding RNA molecules containing 21 to 23 nucleotides. Found in plants, animals and some viruses, miRNAs are involved in RNA silencing and post-transcriptional regulation of gene expression. miRN ...

-mediated

gene silencing Gene silencing is the regulation of gene expression in a cell to prevent the expression of a certain gene. Gene silencing can occur during either transcription or translation and is often used in research. In particular, methods used to silence gen ...

via

RNA interference RNA interference (RNAi) is a biological process in which RNA molecules are involved in sequence-specific suppression of gene expression by double-stranded RNA, through translational or transcriptional repression. Historically, RNAi was known by o ...

. F-box proteins are involved in many plant vegetative and reproduction growth and development. For example, F-box protein-FOA1 involved in

abscisic acid Abscisic acid (ABA) is a plant hormone. ABA functions in many plant developmental processes, including seed and bud dormancy, the control of organ size and stomatal closure. It is especially important for plants in the response to environmental s ...

(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.Kaiser, Peter; Su, Ning-Yuan; Yen, James L.; Ouni, Ikram; Flick, Karin (2006-08-08). "The yeast ubiquitin ligase SCFMet30: connecting environmental and intracellular conditions to cell division". ''Cell Division''. 1: 16. . .^{1/sup>

References

Further reading

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External links

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{{DEFAULTSORT:F-Box Protein
Proteins
Protein domains
Protein structural motifs}