F-box protein explained

Symbol:	F-box
F-box linker domain
Pfam:	PF00646
Pfam Clan:	CL0271
Interpro:	IPR001810
Smart:	SM00256
Prosite:	PS50181
Scop:	1fs2
Membranome Superfamily:	630

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, which mediates ubiquitination of proteins targeted for degradation by the 26S proteasome.

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.^[1] The F-box motif of Skp2, consisting of three alpha-helices, interacts directly with the SCF protein Skp1.^[2] 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.^[3]

Function

F-box proteins have also been associated with cellular functions such as signal transduction and regulation of the cell cycle.^[4] In plants, many F-box proteins are represented in gene networks broadly regulated by microRNA-mediated gene silencing via RNA interference.^[5] 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.^[6] ACRE189/ACIF1 can regulate cell death and defense when the pathogen is recognized in the Tobacco and Tomato plant.^[7]

In human cells, under high-iron conditions, two iron atoms stabilise the F-Box FBXL5 and then the complex mediates the ubiquitination of IRP2.^[8]

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.^{[9] [11]}

Further reading

• Ho M, Tsai P, Chien C . F-box proteins: the key to protein degradation. . J Biomed Sci . 13 . 2 . 181–91 . 2006 . 16463014 . 10.1007/s11373-005-9058-2. free .

Notes and References

1. Bai C, Sen P, Hofmann K, Ma L, Goebl M, Harper JW, Elledge SJ. "SKP1 connects cell cycle regulators to the ubiquitin proteolysis machinery through a novel motif, the F-box". Cell 86 263-74 1996.
2. Bai C, Sen P, Hofmann K, Ma L, Goebl M, Harper JW, Elledge SJ (July 1996). "SKP1 connects cell cycle regulators to the ubiquitin proteolysis machinery through a novel motif, the F-box". Cell. 86 (2): 263–74. . .
3. 2000. The F-box protein family. Genome Biol.. 1. 5. REVIEWS3002. 10.1186/gb-2000-1-5-reviews3002. 138887. 11178263. Kipreos ET, Pagano M . free .
4. Craig KL, Tyers M . The F-box: a new motif for ubiquitin dependent proteolysis in cell cycle regulation and signal transduction . Prog. Biophys. Mol. Biol. . 72 . 3 . 299–328 . 1999 . 10581972 . 10.1016/S0079-6107(99)00010-3. free .
5. Jones-Rhoades MW, Bartel DP, Bartel B . MicroRNAS and their regulatory roles in plants . Annu Rev Plant Biol . 57 . 19–53 . 2006 . 16669754 . 10.1146/annurev.arplant.57.032905.105218 .
6. Peng, Juan; Yu, Dashi; Wang, Liqun; Xie, Minmin; Yuan, Congying; Wang, Yu; Tang, Dongying; Zhao, Xiaoying; Liu, Xuanming (June 2012). "Arabidopsis F-box gene FOA1 involved in ABA signaling". Science China Life Sciences. 55 (6): 497–506. . ISSN 1869-1889. PMID 22744179.
7. Ha, Van Den Burg; Tsitsigiannis, D. I.; Rowland, O; Lo, J; Rallapalli, G; Maclean, D; Takken, F. L.; Jones, J. D. (2008). "The F-box protein ACRE189/ACIF1 regulates cell death and defense responses activated during pathogen recognition in tobacco and tomato". Plant Cell. 20 (3): 697.
8. Moroishi, T; Nishiyama, M; Takeda, Y; Iwai, K; Nakayama, K. I. (2011). "The FBXL5-IRP2 axis is integral to control of iron metabolism in vivo". Cell Metabolism. 14 (3): 339.
9. 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. . .