Systematic analysis and nomenclature of mammalian F-box proteins.
By Jianping Jin, Timothy Cardozo, Ruth C. Lovering, Stephen J. Elledge, M. Pagano, J. Harper. Genes & Development, 2004
722 citations recorded by the source corpus.
Much of the targeted protein ubiquitylation that occurs in eukaryotes is performed by cullin-based E3 ubiquitin ligases, which form a superfamily of modular E3s. The best understood cullin-based E3 is the SCF ubiquitin ligase (Feldman et al. 1997; Skowyra et al. 1997), which is composed of a modular E3 core containing CUL1 and RBX1 (also called ROC1), and a substrate specificity module composed of SKP1 and a member of the F-box family of proteins (Cardozo and Pagano 2004). The CUL1/RBX1 complex functions as a scaffold to assemble the E2 ubiquitin conjugating enzyme with the substrate specificity module (Zheng et al. 2002). CUL1 interacts with RBX1 through its C terminus and with SKP1 through its N terminus. The interaction of F-box proteins with SKP1 occurs through the F-box motif, an ∼40-amino acid motif first identified in budding yeast Cdc4p and human cyclin F, the latter giving the name to the entire family (Bai et al. 1996). F-box proteins contain additional protein interaction domains that bind ubiquitylation targets. The overall architecture of SCF complexes is conserved in the superfamily of SCF-like ubiquitin ligases that use cullin proteins as a scaffold. All cullins characterized to date (CUL1-5) are known to interact with RBX1 or RBX2 but use distinct specificity modules, which generally display structural and functional similarities with the SKP1/F-box protein module. For example, CUL2 and CUL5 are known to interact with the SKP1-like protein elongin C, which, in turn, interacts with F-box protein-like specificity factors called BC/SOCS-box proteins (Deshaies 1999; Guardavaccaro and Pagano 2003). In addition, CUL3 interacts with the BTB/POZ family of proteins, which appear to merge the functions of SKP1 and the F-box protein into a single polypeptide (Furukawa et al. 2003; Geyer et al. 2003; Pintard et al. 2003; Xu et al. 2003), with the BTB domain displaying structural relationships with SKP1 (Schulman et al. 2000; Xu et al. 2003). Cul4 forms a complex wherein DDB1/DDB2 and CSA proteins appear to function as substrate specificity modules (Groisman et al. 2003). Thus, the current expectation is that all cullin-containing ligases will share the modular nature of the original SCF family of ligases.
Subfields: Genetics, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/3508a89b46248cdc029e7b469aedaafc3c83c6d4
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Citations in the corpus
- Genome-Wide and Functional Annotation of Human E3 Ubiquitin Ligases Identifies MULAN, a Mitochondrial E3 that Regulates the Organelle's Dynamics and Signaling (2008, background): “Complete or partial annotation of some of the listed families had been previously reported: general [3,32], TRIM [15,33,34], RBR [16,35,36], BTB [37,38] and F box [39].”
- Structure and function of WD40 domain proteins (2011, background): “WD40, and LRR (leucine-rich repeats, and others) ( Jin et al., 2004 ).”
- Deregulated proteolysis by the F-box proteins SKP2 and β-TrCP: tipping the scales of cancer (2008, background): “Sixty-nine F-box proteins have been identified in human”
- The ubiquitin–26S proteasome system at the nexus of plant biology (2009, background): “By comparison, humans and mice contain only 68 and 74 genes that encode recognizable F-box motifs, respectivel”
- The age of crosstalk: phosphorylation, ubiquitination, and beyond. (2007, background): “Nevertheless, other members of the 68 member F box protein family ( Jin et al., 2004 ) will undoubtedly be found to recognize target proteins in a PTM-dependent manner, as will other types of CRLs, which utilize distinct types of substrate specificity subunits (e.g., SOCS, BTB, and DDB1 proteins).”