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FLASH GENE
Symbol CCND1 contributors: mct/ - updated : 02-08-2021
HGNC name cyclin D1
HGNC id 1582
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • cyclin C terminal domain
  • cyclin N terminal domain
    • HOMOLOGY
    interspecies homolog to murine Ccnd1
    Homologene
    FAMILY
  • cyclin family
  • cyclin D subfamily
    • CATEGORY regulatory
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria,outer
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,nucleoplasm
    text localized at the outer mitochondrial membrane
    basic FUNCTION
  • regulator of progression through G1 phase during the cell cycle 1, involved with CDK4 in phosphorylating retinoblastoma protein
  • involved in normal regulation of the cell cycle and plays an important role in the transition from G1 to S phase of the cell cycle
  • cytosolic cyclin D1 is able to regulate apoptosis by interaction with BAX in low-dose ionizing radiation -induced adaptive resistance
  • STAT5A-regulated transcription
  • playing a crucial role in adipocyte differentiation by regulating mitotic clonal expansion
  • key molecule for transition between the G1 and S phases of the cell-cycle, and amplification or overexpression of cyclin D1 plays pivotal roles in the development of several human cancers
  • provides a transcriptional switch that allows the tumor suppressor activity of RUNX3 to be repressed in cancer cells
  • non-canonical transcriptional function of cyclin D1 may contribute to cancer formation
  • key role for cyclin D1 in cellular proliferation, angiogenesis, and cellular migration
  • inhibits mitochondrial activity in B cells
  • CCND1-CDK4 axis is not only critical in glial tumor cells but also in stromal-derived cells in the surrounding tumor microenvironment that are vital to sustain tumor outgrowth
  • plays significant roles in cell cycle entry and migration
  • key mediator of hepatocyte cell cycle progression
  • represses MLXIPL and HNF4A function in hepatocytes via CDK4-dependent and -independent mechanisms
  • is a critical regulator of cell proliferation and its overexpression has been linked to the development and progression of several malignancies
    • CELLULAR PROCESS cell cycle, checkpoint
    PHYSIOLOGICAL PROCESS
    text cytokinesis
    PATHWAY
    metabolism
    signaling
    a component
  • component of the core cell cycle machinery
  • CCND1-CDK4 axis is not only critical in glial tumor cells but also in stromal-derived cells in the surrounding tumor microenvironment that are vital to sustain tumor outgrowth
  • CIRBP forms a complex together with DYRK1B and CCND1
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • target of activating factor 2 (ATF2) in chondrocytes
  • downstream target of BRAF
  • communication between ATM and cyclin D1 may be required for maintenance of genomic integrity achieved by rapid arrest of the cell-cycle, and that disruption of this crosstalk may increase susceptibility to cancer
  • interacting with INSM1 (interaction could disrupt CDK4 binding during the normal cell cycle)
  • CDC27 directs CCND1 to alternative degradation by APC/C
  • CCND1–RUNX3 interaction interferes with the RUNX3–EP300 interaction, leading to the inhibition of transcriptional activation by RUNX3, downregulation of CDKN1A expression, and the blocking of the RUNX3-dependent inhibition of cancer cell proliferation
  • interacting with SSB (role of SSB in cell proliferation and CCND1 expression demonstrating for the first time an overexpression of the RNA-binding protein SSB in solid tumors.)
  • bound to a voltage-dependent anion channel through its central domain, and it competes with hexokinase 2 for binding to this channel
  • directly binds RAD51, and CCND1-RAD51 interaction is induced by radiation
  • inhibits NFKB transcriptional activity through a corepressor function that can be reverted by over-expressing RAC3
  • YY1 inhibited CDKN1A complex formation with CDK4 and CCND1
  • inhibited the activity of MLXIPL by regulating the glucose-sensing motif of this transcription factor
  • direct relationship between USP18 and CCND1 (but not cyclin E) expression
  • CARD10 contributes to malignant cell growth by facilitating cell cycle progression through NFKB mediated upregulation of CCND1
  • FAM60A promotes the retention of HDAC1 but not SIN3A at the CCND1 promoter in asynchronously growing cells
  • PAX2 is a positive regulator of expression of CCND1 (PAX2 induces CCND1 through AP1)
  • ROCK1 and ROCK2 could promote vascular smooth muscle cells (VSMC) proliferation through ERK nuclear translocation, regulating the expression of PCNA and cyclin D1 protein
  • EYA1 phosphatase regulates cell-cycle control via transcriptional complex formation at the CCND1 promoter
  • NUMBL could decrease the expression of TRAF6, CCND1, and MMP9 and increase the expression of CASP3
  • 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
  • CCND1, a key mediator of cell growth during tissue regeneration, is a GLI1 transcriptional target, binding to the CCND1 promoter and regulating its activity and expression
  • nuclear IGF2BP3-HNRNPM complex is important for the efficient synthesis of CCND1, CCND3 and CCNG1 and for the proliferation of human cancer cells
  • novel function of CCND1 in promoting cell cycle progression by enhancing STK38/STK38L kinase activity independent of CDK4
  • CSF2 accelerated the G1/S phase transition in endothelial progenitor cells (EPCs) by upregulating the expression of CCND1 and CCNE1
  • up-regulation of CCND1 and BCL2A1 by insulin is involved in osteoclast proliferation
  • MYF5 enhances early myogenesis in part by coordinately elevating CCND1 transcription and CCND1 mRNA translation
  • ZNRF2 appeared to augment MTOR and its downstream targets CCND1 and CDK in non-small cell lung cancer cells
  • 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 CCNE
  • SHCBP1 promoted cell cycle progression by regulating the CDK4&
    • 8209;CCND1 cascade and suppressed CASP3, caspase PARP&
    8209;dependent apoptotic pathways
  • TCEAL7 regulates CCND1 expression through MYC-binding E-box sequences
  • ZNF322 positively regulates transcription of alpha-adducin (ADD1) and cyclin D1 (CCND1) to promote tumorgenicity of lung cancer
  • NFIC may contribute to postnatal chondrocyte proliferation by inhibiting CDKN1A expression and by increasing the stability of CCND1 protein
  • USP27X binds to and stabilizes CCND1 in a catalytically dependent manner by negatively regulating its ubiquitination
    • cell & other
    REGULATION
    activated by promoter activated by JUN
    POU5F1, that can upregulate BIRC5 and CCND1 expression by increasing their promoter activity, and these factors collusively promotes hepatocellular carcinoma cell proliferation
    induced by Hedgehog for regulating cell growth and proliferation
    repressed by JUNB
    Other regulated by SNAI2 (SNAI2 regulates the turnover rates of several key proteins like CCND1 by repressing the ubiquitin-conjugating enzyme UBE2D3)
    ASSOCIATED DISORDERS
    corresponding disease(s) BCL1
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral fusion      
    fused with TACSTD2 in cancer cells, fused with Igh in t(11;14) (q13;q32)
    tumoral   amplification    
    amplified in mantle cell lymphoma(same as BCL1, D11S287E), endometrial cancer
    tumoral     --low  
    in T-cell leukemia
    tumoral   translocation    
    t(6;11)(p21;q13), t(1;11)(p13;q13), t(7;11)(q11.2;q13), and t(5;11)(q35; q13) in renal oncocytoma
    tumoral     --over  
    in parathyroid adenoma, breast (stimulatory effect of estradiol and prolactin) carcinoma
    tumoral   amplification    
    coamplified with SHANK2, and CTT1 in oral squamous cell carcinoma
    tumoral   deletion    
    deletion in mantle cell lymphoma, associated with increased proliferation rate and shorter survival
    tumoral   translocation    
    in parathyroid adenomas
    tumoral   amplification    
    in breast cancer, alone or with PPFIA1
    constitutional     --over  
    perturbs DNA replication and induces replication-associated DNA double-strand breaks in acquired radioresistant cells
    Susceptibility
  • to colorectal carcinoma (non polyposis)
  • to lung cancer in smokers from north India
  • to HELLP syndrome
    • Variant & Polymorphism
  • polymorphism modifying the age at onset of colorectal cancer
  • A870G gene polymorphisms may increase the risk of lung cancer in smokers from north India
    • Candidate gene polymorphisms N363S associated with the development of HELLP syndrome
    Marker
  • biomarker for thyroid cancer exhibiting differences in the correlation coefficients between benign and malignant samples that indicate its discriminatory power
    • Therapy target
    SystemTypeDisorderPubmed
    cancer  
    targeting CCND1 may be beneficial also in retinoblastoma-negative cancers which are currently thought to be unaffected by CCND1 inhibition
    cancer  
    targeting CCND1 is a promising strategy for preventing tumor progression and combating therapy resistance in cancer
    ANIMAL & CELL MODELS