Table 1.
Control of key dimensions of cellular life by F-box proteins
| F-box protein |
Substrate | Function of substrate | Mechanism of degron regulation |
|---|---|---|---|
| Differentiation and development | |||
| βTrCP | β-catenin | WNT signalling | Phosphodegron, priming phosphorylation |
| βTrCP | REST | Neural differentiation, cell cycle | Phosphodegron |
| βTrCP | SNAIL | Epithelial–mesenchymal transition | Phosphodegron, priming phosphorylation |
| FBXL14 | SNAIL | Epithelial–mesenchymal transition | Unknown |
| FBXO11 | BCL6 | B cell development | Unknown |
| FBXO11 | CDT2 | DNA replication, seam cells (in worms) | Blocked by phosphorylation |
| FBXO32 | MyoD | Muscle cell differentiation | Unknown |
| FBXW7 | CEBPα | Adipocyte differentiation | Phosphodegron |
| FBXW7 | SREBP1 | Adipocyte differentiation | Phosphodegron |
| Cell division | |||
| βTrCP | BORA | Mitotic signalling | Phosphodegron |
| βTrCP | EMI1 | APC/C inhibitor | Phosphodegron |
| βTrCP | PLK4 | Centriole duplication | Phosphodegron |
| βTrCP | WEE1 | Kinase, CDK inhibitor | Phosphodegron |
| Cyclin F | CP110 | Centriole duplication | Unmodified, localization dependent |
| Cyclin F | RRM2 | dNTP production | Restricted access |
| FBXW5 | EPS8 | Actin remodelling | Unknown |
| FBXW7 | Cyclin E | Cell cycle | Phosphodegron |
| SKP2 | p27 | CDK inhibitor | Cofactor-dependent |
| Cell death and survival | |||
| βTrCP | BIMEL | Apoptosis | Phosphodegron |
| βTrCP | IκB | Inhibitor of NF-κB signalling | Phosphodegron |
| FBXO7 | cIAP1 | Apoptosis inhibitor | Unknown |
| FBXW7 | MCL1 | Survival factor | Phosphodegron |
| FBXW7 | p100 | Non-canonical NF-κB signalling | Phosphodegron |
| Cell growth | |||
| βTrCP | DEPTOR | Inhibitor of mTOR | Phosphodegron, priming phosphorylation |
| βTrCP | PDCD4 | Inhibits protein synthesis | Phosphodegron |
| FBXO9 | TEL2 and TTI1 | mTOR signalling | Phosphodegron |
| FBXW7 | JUN | Mitogenic signalling | Phosphodegron |
| FBXW7 | MYC | Cell proliferation | Phosphodegron |
| Signalling | |||
| βTrCP | CDC25A | Phosphatase, CDK activator | Phosphodegron |
| βTrCP | PER1 and PER2 | Circadian rhythm | Phosphodegron |
| FBXL2 | p85β | PI3K signalling | Blocked by phosphorylation |
| FBXL3 | CRY1 and CRY2 | Circadian rhythm | Domain recognition, possibly ligand |
| FBXL5 | IRP2 | Iron homeostasis | Unknown |
APC/C, anaphase-promoting complex (also known as the cyclosome); βTrCP, β-transducin repeat-containing protein; BCL6, B cell lymphoma 6; BIMEL, BCL-2-interacting mediator of cell death extra long; BORA, aurora borealis; CDK, cyclin-dependent kinase; CEBPα, CCAAT-enhancer-binding protein-α; cIAP1, cellular inhibitor of apoptosis 1; CP110, centrosomal protein 110; CRY, cryptochrome; DEPTOR, DEP-domain containing mTOR-interacting protein; EMI1, early mitotic inhibitor 1; EPS8, EGFR kinase substrate 8; FBXL, F-box and Leu-rich repeat; FBXO, F-box only; FBXW, F-box and WD40 domain; IκB, inhibitor of κB; IRP2, iron-regulatory protein 2; MCL1, myeloid cell leukaemia sequence 1; mTOR, mammalian target of rapamycin; MyoD, myoblast determination; NF-κB, nuclear factor-κB; PDCD4, programmed cell death 4; PER, period; PLK4, Polo-like kinase 4; REST, RE1-silencing transcription factor; RRM2, ribonucleotide reductase subunit M2; SREBP1, sterol regulatory element-binding protein 1; SKP2, S phase kinase-associated protein 2; TEL2, telomere length regulation protein 2; TTI1, TELO2-interacting protein 1.