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FLASH GENE
Symbol CUL1 contributors: mct/pgu - updated : 20-02-2018
HGNC name cullin 1
HGNC id 2551
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a globular segment binding RBX1
  • a stalk bound to SKP1-F-box protein
  • a conserved C terminal sequence required for nuclear accumulation
    • conjugated Other
    mono polymer heteromer , dimer
    HOMOLOGY
    interspecies homolog to C.elegans CUL 1
    ortholog to murine Cul1
    ortholog to rattus Cul1_predicted
    Homologene
    FAMILY
  • cullin family
    • CATEGORY chaperone/stress , regulatory
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,nucleoplasm
    basic FUNCTION
  • acting as a negative regulator of the cell cycle
  • targeting protein for ubiquitin dependent proteolysis
  • may function as a tumor suppressor by regulating PLK4 protein levels and thereby restraining excessive daughter centriole formation at maternal centrioles
  • matrix degrading enzyme known to be involved in the remodelling of extracellular matrix proteins
  • play a key role in tumour progression and its presence is associated with poor clinical outcome for several different types of tumours
  • scaffold protein in cullin-based ubiquitin ligases, playing an important role in early embryonic development
  • promotes likely trophoblast cell invasion and dysregulation of CUL1 expression may be associated with preeclampsia
  • is a scaffold protein of the ubiquitin E3 ligase SKP1/CUL1/RBX1/F-box protein complex, which ubiquitinates a broad range of proteins involved in cell-cycle progression, signal transduction, and transcription
  • is a scaffold protein of the ubiquitin E3 ligase SKP1/CUL1/RBX1/F-box protein complex, which ubiquitinates a broad range of proteins involved in cell-cycle progression, signal transduction, and transcription
  • unneddylated CUL1 is another central player involved in maintenance of the adaptor module pool through the formation of CUL1-SKP1-F-box complexes and promotion of rapid SCF (SKP1-CUL1-F-box protein) assembly
    • CELLULAR PROCESS cell cycle, division
    cell cycle, checkpoint
    cell life, proliferation/growth
    cell life, cell death/apoptosis
    protein, ubiquitin dependent proteolysis
    cell migration & motility
    PHYSIOLOGICAL PROCESS
    text G1/S transition
    PATHWAY
    metabolism
    signaling
    a component
  • constituent of a core ubiquitin-ligase SCF (SKP1, CUL1, SKP2), RRX1 with CIP1/WAF1, CDC34 and cyclin D(CCND)
  • hyper-neddylated
  • complex between GLMN, RBX1, and a fragment of CUL1
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • targeting G1 cell cycle regulators (NAF1, CDC34, CCND) for ubiquitin-dependent proteolysis required with RBX1 for nuclear localization of NEDD8
  • EIF3E and the COP9 signalosome play opposing roles in regulation of cullin neddylation
  • binds to the components of the neddylation pathway (DCUN1D1, UBE2M, and CAND1)
  • binding CAND1
  • interacting with PLK4 (is critical for the degradation of active PLK4 following deregulation of cyclin E/cyclin-dependent kinase 2 activity, as is frequently observed in human cancer cells, as well as for baseline PLK4 protein stability)
  • critical for the ubiquitin-dependent suppression of the KDM4A-dependent faster S phase progression
  • DRG2 was a substrate of a SKP1-CUL1-F-box E3 ligase complex and inhibition the function of Cullin1 prevented the degradation of DRG2 during apoptosis
  • SF3B3 overexpression reduces the binding of adaptor protein SKP1 and substrate receptor SKP2 to CUL1, whereas it has no effect on CAND1 binding to CUL1
  • CUL1 promoted MTOR activity and cap-dependent translation by enhancing the ubiquitination and degradation of DEPTOR
  • YTHDF2 promotes mitotic entry and is regulated by cell cycle mediators (CUL4A, DDB1, CUL1, SKP2)
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    significantly associated with high-grade tumours and poor prognosis
    tumoral     --over  
    in renal cell carcinoma (RCC)
    tumoral     --over  
    in melanoma, enhancing melanoma cell proliferation by promoting G1-S phase transition
    tumoral     --over  
    positively associated with lymph node metastasis and tumor diameter
    tumoral     --over  
    significantly increased in human glioma, and it may be involved in proliferation, migration and invasion of glioma cells
    Susceptibility
  • may affect the susceptibility of rheumatoid arthritis (RA) via altering lymphocyte signal transduction
    • Variant & Polymorphism other
  • possible role of CUL1 variation(s) in RA and its response to methotrexate
    • Candidate gene
    Marker
  • its expression may therefore be crucial for the prediction of disease outcome in breast cancer patients
  • CUL1 may be an important prognosis marker for human hepatocellular carcinoma (HCC)
  • may serve as promising prognostic markers in colorectal cancer (CRC) patients
    • Therapy target
    SystemTypeDisorderPubmed
    cancerurinary 
    CUL1 may constitute a potential therapeutic target in enal cell carcinoma (RCC)
    ANIMAL & CELL MODELS
  • dysregulation of cyclin E and early embryonic lethality in CUL1-/-
  • cul1-/- sequestrate and inactivate Skp1 leading to genetic instability and neoplastic transformation