F-box only protein 11 is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

that in humans is encoded by the ''FBXO11''

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

Function

This gene encodes a member of the

F-box protein 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 co ...

family which is characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in

phosphorylation In biochemistry, phosphorylation is described as the "transfer of a phosphate group" from a donor to an acceptor. A common phosphorylating agent (phosphate donor) is ATP and a common family of acceptor are alcohols: : This equation can be writ ...

-dependent

ubiquitination 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 19 ...

. The F-box proteins are divided into 3 classes: Fbws containing

WD-40 domain 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, Fbls containing

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

s, and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene belongs to the Fbxs class. Alternatively spliced transcript variants encoding distinct isoforms have been identified for this gene. FBXO11 is conserved from

nematode The nematodes ( or ; ; ), roundworms or eelworms constitute the phylum Nematoda. Species in the phylum inhabit a broad range of environments. Most species are free-living, feeding on microorganisms, but many are parasitic. Parasitic worms (h ...

s to mammals, and both human FBXO11 and its worm ortholog (DRE-1) form functional SCF

ubiquitin ligase A ubiquitin ligase (also called an E3 ubiquitin ligase) is a protein that recruits an E2 ubiquitin-conjugating enzyme that has been loaded with ubiquitin, recognizes a protein substrate, and assists or directly catalyzes the transfer of ubiquitin ...

complexes. By binding to and mediating the degradation of its substrate proteins, FBXO11 plays important roles in regulating cell cycle regulation,

tumorigenesis Carcinogenesis, also called oncogenesis or tumorigenesis, is the formation of a cancer, whereby normal cells are transformed into cancer cells. The process is characterized by changes at the cellular, genetic, and epigenetic levels and abn ...

, and tumor cell

metastasis Metastasis is a pathogenic agent's spreading from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, ...

. Well established targets of FBXO11 include

BCL6 Bcl-6 (B-cell lymphoma 6) is a protein that in humans is encoded by the ''BCL6'' gene. BCL6 is a master transcription factor for regulation of T follicular helper cells (TFH cells) proliferation. BCL6 has three evolutionary conserved structural d ...

, CDT2, and

Snail A snail is a shelled gastropod. The name is most often applied to land snails, terrestrial molluscs, terrestrial pulmonate gastropod molluscs. However, the common name ''snail'' is also used for most of the members of the molluscan class Gas ...

Clinical significance

Inactivation of FBXO11-mediated BCL6 degradation has been shown to contribute to abnormal germinal-center formation and tumorigenesis. The ''Caenorhabditis elegans'' DRE-1/FBXO11 was reported to target the conserved transcription factor BLMP-1 for proteasomal degradation, and thereby regulates developmental timing and maturation.Dev Cell. 2014 Mar 31;28(6):697-710. doi: 10.1016/j.devcel.2014.01.028. DRE-1/FBXO11-dependent degradation of BLMP-1/BLIMP-1 governs C. elegans developmental timing and maturation. Horn M, Geisen C, Cermak L, Becker B, Nakamura S, Klein C, Pagano M, Antebi A. The gene encoding FBXO11 was found to be deleted or mutated in multiple diffuse large B cell lymphoma (DLBCL) cell lines, and this inactivation of FBXO11 contributes to increased levels BCL6 and subsequently DLBCL pathogenesis. FBXO11 mutations were also identified in other human cancers, such as colon, lung, ovary, and head and neck tumors. In mice, a homozygous mutation of FBXO11 results in

cleft palate A cleft lip contains an opening in the upper lip that may extend into the nose. The opening may be on one side, both sides, or in the middle. A cleft palate occurs when the palate (the roof of the mouth) contains an opening into the nose. The ...

defects, facial clefting, and perinatal lethality. Moreover,

haploinsufficient Haploinsufficiency in genetics describes a model of dominant gene action in diploid organisms, in which a single copy of the wild-type allele at a locus in heterozygous combination with a variant allele is insufficient to produce the wild-type ...

mutant alleles cause

otitis media Otitis media is a group of Inflammation, inflammatory diseases of the middle ear. One of the two main types is acute otitis media (AOM), an infection of rapid onset that usually presents with ear pain. In young children this may result in pullin ...

, a disorder that affects approximately 15% of children.

Function

Clinical significance

References

Further reading