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FLASH GENE
Symbol CCNE1 contributors: mct/npt - updated : 09-11-2018
HGNC name cyclin E1
HGNC id 1589
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a modular centrosomal-targeting domain essential for promoting S phase entry in a CDK2-independent manner
    • HOMOLOGY
    Homologene
    FAMILY
  • cyclin family
  • cyclin E subfamily
    • CATEGORY regulatory
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    intracellular,nucleus,nucleoplasm
    text
  • localization of cyclin E on centrosomes is mediated by a 20-amino acid domain termed the centrosomal localization sequence (CLS)(Ferguson 2008)
  • expressed at the G 1/S phase transition of the cell cycle to drive the initiation of DNA replication and degraded during S/G2M
    • basic FUNCTION
  • regulating G1 to S transition of the cell cycle and promoting DNA synthesis
  • phosphorylating NPME, in association with CDK2, leading to the initiation of centrosome duplication
  • plays an essential role in the G(1)/S cell cycle transition and DNA replication (Mazumder 2007)
  • in addition to their function as CDK activators-CCNE1 play kinase-independent functions in cell-cycle progression (Geng 2007)
  • implicated in regulating centrosome duplication (Ferguson 2008)
  • cyclin E-dependent localization of MCM5 regulates centrosome duplication (Ferguson 2008)
  • ectopic expression of CCNE1 enhances the ubiquitin-dependent proteolysis of CCNE2, suggesting a potential cross-talk in the regulation of E-type cyclin activity
  • important regulator of cell-cycle progression (Potemski 2009)
  • role of E2F1-CCNE1-CCNE2 circuit in coronary smooth muscle cell proliferation
  • key role for CCNE1, CCNE2 in promoting megakaryocyte entry into S phase and hence, increase in the number of cell cycling cells and in augmenting polyploidization
  • role for CCNE1, CCNE2 in the development and function of the mammalian central nervous system and its subcellular localization in neurons is important
  • in urothelial cells, cyclin E is recruited to the nuclear matrix as cells differentiate
  • by causing DNA damage, accumulation of CCNE1 might trigger the keratinocyte mitosis checkpoints and in turn, terminal differentiation
  • overexpression of CCNE1 in human basal keratinocytes induced a mitosis block, re-replication and differentiation
  • TEAD1 may mediate muscle development through its target genes, MRPL21, NDUFA6 and CCNE1
  • CCNE1 drives the initiation of DNA replication, and deregulation of its periodic expression leads to mitotic delay associated with genomic instability
  • CCNE2 induction of genomic instability by a mechanism distinct from CCNE1 indicates that these two proteins have unique functions in a cancer setting
  • regulates the cell cycle transition from G1 to S phase and is degraded before entry into G2 phase
  • CCNE1, CCNE2 control chromosome pairing, telomere stability and CDK2 localization in male meiosis
  • CCNE1/REL and TUBA1B/ESR1 might play pivotal roles in the occurrence and development of Postmenopausal osteoporosis
    • CELLULAR PROCESS cell cycle
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    CCNE1/CDK2/NPAT/HINFP pathway that is required for cell cycle-dependent activation of histone H4 genes at the G1/S phase transition (Xie 2009)
    a component
  • complexing with CDK2
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • directly interact with and colocalize on centrosomes with the DNA replication factor MCM5 in a centrosomal localization sequence-dependent but CDK2-independent manner
  • association with XRCC6 induces the dissociation of BAX from XRCC6, followed by BAX activation (Mazumder 2007)
  • DDX3X is critical for translation of CCNE1 mRNA, which provides an alternative mechanism for regulating CCNE1 expression during the cell cycle
  • direct link between CCNE1, CCNE2 and HIF1A activities in mammary epithelial cells and implicating HIF1A is a mediator of proliferation-independent phenotypes associated with high CCNE1, CCNE2 expression in some human breast cancers
  • BMI1 has a critical role in stabilizing CCNE1 by repressing the expression of FBXW7, a substrate-recognition subunit of the SCF E3 ubiquitin ligase that targets CCNE1 for degradation
  • YWHAE regulates cardiogenesis and growth of the compact ventricular myocardium by modulating the cardiomyocyte cell cycle via both CCNE1 and CDKN1B
  • RSF1 interacts and collaborates with CCNE1 in neoplastic transformation and TP53 mutations are a prerequisite for tumour-promoting functions of the RSF1/CCNE1 complex
  • KDM5A upregulated expression of CCND1 and CCNE1 while suppressing the expression of cyclin-dependent kinase inhibitor p27 (CDKN1B), each contributing to KDM5A-mediated cell proliferation
  • RHOBTB3, a Golgi-associated, Rho-related ATPase, regulates the S/G2 transition of the cell cycle by targeting CCNE for ubiquitylation
  • novel role for CCNE1 beyond G1/S and into S/G2 phase, most likely by inducing the expression of subsequent CCNA2 and CCNB1 through LIN9
  • CSF2 accelerated the G1/S phase transition in endothelial progenitor cells (EPCs) by upregulating the expression of CCND1 and CCNE1
  • CDKN1A/CCNE1 pathway is crucial in modulating the anticlastogenic function of BMI1
  • HOXA7 stimulates human hepatocellular carcinoma proliferation through CCNE1/CDK2
  • CIAPIN1 played an important role in the proliferation of liver cancer cells through increasing the expressions of cell cycle related proteins CCND1, CDK2, CDK4, and CCNE1
  • USP27X promoted CCCNE1 stability by negatively regulating its ubiquitination
  • CCNK-dependent, novel phosphorylation site in CCNE1 that disrupts its interaction with CDK2
    • cell & other
    REGULATION
    induced by Hedgehog for regulating cell growth and proliferation
    inhibited by PRMT5
    Other targeted by AGO for ubiquitin-dependent proteolysis
    ubiquitinated in vitro by ago
    regulated by FBXW7
    regulated by CARM1
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in many tumors leading to a deregulated level of protein and kinase activity relative to the cell cycle and inducing chromosome instability
    tumoral     --over  
    significant factor of poor prognosis, especially in the node-positive groupof breast cancer (Potemski 2009)
    tumoral     --over  
    is associated with Stage 4 neuroblastomas and poor prognosis in patients
    tumoral   amplification --over  
    is amplified and overexpressed in osteosarcoma
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • highest positive predictive value for classical Hodgkin lymphoma (cHL)
    • Therapy target
    ANIMAL & CELL MODELS