CUL1

Description

The CUL1 (cullin 1) is a protein-coding gene located on chromosome 7.

Cullin 1, also known as CUL1, is a human protein and gene belonging to the cullin family. This protein plays a crucial role in protein degradation and ubiquitination. As an essential component of the SCF (SKP1-CUL1-F-box protein) E3 ubiquitin ligase complex, it mediates the ubiquitination of proteins involved in cell cycle progression, signal transduction, and transcription. Within the SCF complex, CUL1 acts as a rigid scaffold, organizing the SKP1-F-box protein and RBX1 subunits. It might also contribute to catalysis by positioning the substrate and the ubiquitin-conjugating enzyme. CUL1 is part of a SCF complex composed of CUL1, RBX1, SKP1, and SKP2. It interacts with RNF7. CUL1 also forms a complex with TIP120A/CAND1 and RBX1. The unneddylated form of CUL1 interacts with TIP120A/CAND1, and this interaction negatively regulates the association with SKP1 in the SCF complex. CUL1 also interacts with COPS2.

CUL1 is a core component of multiple cullin-RING-based SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complexes. These complexes mediate the ubiquitination of proteins involved in cell cycle progression, signal transduction, and transcription. SCF complexes and ARIH1 collaborate to ubiquitinate target proteins. Within the SCF complex, CUL1 acts as a rigid scaffold that organizes the SKP1-F-box protein and RBX1 subunits. It may contribute to catalysis by positioning the substrate and the ubiquitin-conjugating enzyme. The E3 ubiquitin-protein ligase activity of the complex depends on the neddylation of the cullin subunit, while the exchange of the substrate recognition component is mediated by TIP120A/CAND1. The functional specificity of the SCF complex is determined by the F-box protein, which acts as the substrate recognition component. For example, SCF(BTRC) and SCF(FBXW11) direct the ubiquitination of CTNNB1 and participate in Wnt signaling. SCF(FBXW11) ubiquitinates phosphorylated NFKBIA. SCF(BTRC) ubiquitinates NFKBIB, NFKBIE, ATF4, SMAD3, SMAD4, CDC25A, FBXO5, and possibly NFKB2. SCF(BTRC) and/or SCF(FBXW11) direct the ubiquitination of CEP68. SCF(SKP2) ubiquitinates phosphorylated CDKN1B/p27kip and regulates G1/S transition. SCF(SKP2) also ubiquitinates ORC1, CDT1, RBL2, ELF4, CDKN1A, RAG2, FOXO1A, and possibly MYC and TAL1. SCF(FBXW7) ubiquitinates CCNE1, NOTCH1 released notch intracellular domain (NICD), and potentially PSEN1. SCF(FBXW2) ubiquitinates GCM1. SCF(FBXO32) ubiquitinates MYOD1. SCF(FBXO7) ubiquitinates BIRC2 and DLGAP5. SCF(FBXO33) ubiquitinates YBX1. SCF(FBXO1) ubiquitinates BCL6 and DTL but does not seem to ubiquitinate TP53. SCF(BTRC) mediates the ubiquitination of NFKBIA at 'Lys-21' and 'Lys-22'; this degradation frees the associated NFKB1-RELA dimer to translocate into the nucleus and activate transcription. SCF(CCNF) ubiquitinates CCP110. SCF(FBXL3) and SCF(FBXL21) ubiquitinate CRY1 and CRY2. SCF(FBXO9) ubiquitinates TTI1 and TELO2. SCF(FBXO10) ubiquitinates BCL2.

CUL1 is also known as -.

Associated Diseases

WES Whole Exome Sequencing