CUL1
CUL1 (cullin 1, also named Cullin-1) is the core scaffold of SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complexes. These complexes direct the ubiquitination of proteins involved in cell cycle progression, signal transduction and transcription. Browse Assay Genie's current range of CUL1 research reagents below, or read on for the biology behind the target.
CUL1 is a core component of multiple cullin-RING-based SCF E3 ubiquitin-protein ligase complexes. Within the complex it acts as a rigid scaffold that organises the SKP1-F-box protein and RBX1 subunits, and it may contribute to catalysis by positioning the substrate and the ubiquitin-conjugating enzyme. SCF complexes also collaborate in tandem with ARIH1 to ubiquitinate target proteins. Ligase activity depends on neddylation of the cullin subunit, while exchange of the substrate recognition component is mediated by TIP120A/CAND1.
Functional specificity comes from the F-box protein that serves as the substrate receptor. SCF(BTRC) and SCF(FBXW11) direct ubiquitination of CTNNB1 and take part in Wnt signalling; SCF(FBXW11) also targets phosphorylated NFKBIA, and degradation of NFKBIA frees the NFKB1-RELA dimer to enter the nucleus and activate transcription. SCF(SKP2) directs ubiquitination of phosphorylated CDKN1B/p27kip and is involved in regulation of the G1/S transition, and also targets CDT1, ORC1 and CDKN1A. SCF(FBXW7) directs ubiquitination of CCNE1 and the NOTCH1 intracellular domain. Other examples include SCF(FBXL3) and SCF(FBXL21) acting on CRY1 and CRY2, SCF(FBXO10) on BCL2, and SCF(FBXO31) on proteins amidated at their C-terminus in response to oxidative stress.
The CUL1 gene encodes a member of the cullin family, listed by HGNC in the cullins and SCF complex core subunit groups. NCBI Gene describes CUL1 as contributing to ubiquitin ligase complex scaffold activity and to SCF-dependent proteasomal protein catabolism, K48-linked ubiquitination and positive regulation of canonical NF-kappaB signalling. It is part of the Parkin-FBXW7-Cul1 complex, is active in the nucleus and is located in the plasma membrane. The mouse ortholog is Cul1.
CUL1 is the scaffold that assembles SKP1, F-box proteins and RBX1 into SCF E3 ligases, making it central to studies of substrate ubiquitination.
SCF(SKP2) and SCF(FBXW7) complexes built on CUL1 target CDKN1B, CDT1 and CCNE1, linking the protein to G1/S transition control.
SCF(BTRC) and SCF(FBXW11) direct ubiquitination of NFKBIA and CTNNB1, placing CUL1 within NF-kappaB and Wnt pathway research.
CUL1 activity depends on cullin neddylation and CAND1-mediated exchange of F-box proteins, a focus for work on E3 ligase regulation.
CUL1 is a core scaffold of SCF E3 ubiquitin-protein ligase complexes. It organises the SKP1-F-box protein and RBX1 subunits so that substrates recognised by the F-box protein can be ubiquitinated, affecting cell cycle progression, signal transduction and transcription.
The HGNC name is cullin 1 and UniProt lists Cullin-1; no aliases or previous symbols are recorded. CUL1 belongs to the cullin family and sits in the HGNC group of cullins and SCF complex core subunits.
A mouse ortholog, Cul1, is recorded for this gene. Related cullin family members include CUL2, CUL3, CUL4A, CUL5 and CUL7, which also act in cullin-RING ligases; check the datasheet of any product for its validated reactivity.
Other cullin family members that form cullin-RING E3 ubiquitin ligase complexes.
Gene and protein annotations from HGNC, NCBI Gene and UniProt Q13616; product specifications from Assay Genie datasheets.