Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Orphanet Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
Symbol CDKN1C contributors: mct/npt/pgu - updated : 06-02-2013
HGNC name cyclin-dependent kinase inhibitor 1C (p57, Kip2)
HGNC id 1786
Corresponding disease
BWS Beckwith-Wiedemann syndrome
IMAS IMAGE syndrome
Location 11p15.4      Physical location : 2.904.449 - 2.906.995
Synonym name
  • cyclin-dependent kinase inhibitor 1C
  • cyclin-dependent kinase inhibitor p57
  • Synonym symbol(s) CDKN5, KIP2, P57, p57KIP2
    DNA
    TYPE functioning gene
    STRUCTURE 2.55 kb     4 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    Binding site   silencer
    text structure silencer sequence in the promoter
    MAPPING cloned Y linked N status confirmed
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    3 - 1943 - 316 - 1996 8640800
    4 - 1776 - 305 - 1996 8640800
    4 - 1771 - 305 - 1996 8640800
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly
    Endocrineadrenal gland   highly Homo sapiensFetal
    Reproductivefemale systemplacenta  highly
     male systemtestis   
    Respiratorylung    
    Urinarykidney    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumskeletal  
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period pregnancy
    Text placenta
    IMPRINTING paternally
    text
  • maternally expressed, partially paternally imprinted
  • PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a CDK inhibitory domain
  • a proline-alanine rich (PAPA), an acidic repeat region
  • a conserved C terminal domain, PCNA-binding domain (pMID: 22634755)
  • HOMOLOGY
    interspecies homolog to murine CdKnc1c
    Homologene
    FAMILY
  • CDK inhibitor (CDI) family
  • CATEGORY enzyme , regulatory , tumor suppressor
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm
    intracellular,nucleus
    basic FUNCTION
  • CDK2, CDK4 inhibitor and involved in the G1 phase arrest
  • critical terminal effector of signal transduction pathways that control cell differentiation
  • intrinsic inhibitor of myelinating Schwann cell differentiation, and its down-regulation is a prerequisite to allow differentiation to progress
  • primarily promotes the intrinsic apoptotic pathways, favoring BAX activation and loss of mitochondrial transmembrane potential, consequent release of cytochrome-c into cytosol, caspase-9 and caspase-3 activation
  • encodes an intrinsic inhibitor of myelinating glial cell differentiation
  • coordinates multiple stages of corticogenesis and exhibits distinct and common activities compared with CDKN1B
  • CDKN1B, CDKN1C cooperate to maintain hematopoietic stem cell quiescence through interactions with HSPA8
  • CDKN1B and CDKN1C control neuronal output for distinct cortical layers by regulating different stages of precursor proliferation
  • able to enhance mitochondrial-mediated apoptosis, and CDKN1C control of actin cytoskeleton dynamics is responsible for its mitochondrial pro-apoptotic effect
  • in primary hepatocellular carcinoma, HES1 protein expression inversely correlates with CDKN1C/P57 mRNA levels
  • intrinsic regulator of late gliogenesis and in oligodendroglial precursor cells its inhibition leads to accelerated maturation
  • regulates glial fate decision in adult neural stem cells
  • AHI1 and CDKN1C exhibit opposite expression patterns, where AHI1 is expressed in poor and intermediate prognosis patients, while CDKN1C is expressed in favourable prognosis patients
  • CELLULAR PROCESS cell life, differentiation
    PHYSIOLOGICAL PROCESS
    text
  • regulator of cell cycle
  • controlling differentiation of skeletal muscle and alveoli in the lung in parallel with P21 and myogenin
  • PATHWAY
    metabolism
    signaling signal transduction
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacts with LIMK1 (down-regulation could regulate the subcellular distribution of LIMK1 affecting the equilibrium of enzymes and regulators that control cytoskeletal dynamics)
  • CDKN1C interacts with the actin cytoskeleton modifying enzyme, LIM-kinase 1 (LIMK1) but not LIMK2 (CDKN1C control of LIMK1 ultimately affects cell mobility negativel)
  • E2F1-CDKN1C interaction mediated by two E2F domains (a central E2F1 domain interacts directly with CDKN1C, whereas a C-terminal E2F1 domain interacts with CDKN1C via interaction with Rb)
  • drives potentially muscle differentiation through a positive feedback loop with MYOD1
  • EZH2 acts as an oncogene in tumorigenesis of ovarian cancer with the possible mechanism to suppress the anti-oncogene CDKN1C
  • interacts with both CDKN1C and CDKN1B and the subcellular localization of HSPA8 was critical to maintain HSC (hematopoietic stem cell) cycle kinetics
  • LIMK1, the enzyme mediating CDKN1C effect on the actin cytoskeleton, was required for CDKN1C death promoting effect
  • CDKN1C is a target of transcriptional repression by the NOTCH effector, HES1
  • cell & other
    REGULATION
    activated by E2F1 (E2F1 activates transcription of two members of the CDKN1 family CDKN1B and CDKN1C)
    Phosphorylated by MAPK14 (cell survival to various stresses depends on CDKN1C phosphorylation by MAPK14 that inhibits CDK activity)
    Other regulation by post-transcription
    downregulation of CDKN1C is involved in the cell cycle progression of vascular smooth muscle cells
    monoubiquitination might represent a CDKN1C modification that promotes (or inhibits) its interaction with an as yet unknown partner
    ASSOCIATED DISORDERS
    corresponding disease(s) BWS , IMAS
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional germinal mutation      
    in approximatively 5p100 of sporadic Beckwith-Wiedemann syndrome and 40 p100 of familial cases
    constitutional     --low  
    (imprinting domain involving KCNQ10T1/CDKN1C) in BWS
    tumoral     --low  
    in sporadic cases without deleted mutation of Beckwith Wiedemann and in large colorectal tumor
    constitutional     --low  
    in biparental complete hydatiform mole
    constitutional        
    (by silencing) associated or not with hypomethylation of KCNQ1OT1 in BWS
    tumoral        
    silenced by loss of methylation in esophageal cancer (associated with loss of CpG and histone H3 lysine 9 methylation at KCNQ1OT1)
    tumoral     --low  
    in urothelial carcinomas
    constitutional     --low  
    transiently down-regulated under inflammatory, demyelinating, pathophysiological conditions before the onset of multiple sclerosis remission
    tumoral     --low  
    associated with poor disease outcome in patients with cutaneous T-cell lymphoma, while upregulation of AHI1 shows a weak association with aggressive disease course
    tumoral     --over  
    in human retinoblastomas
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    neurologyneurodegenerative 
    silencing CDKN1C gene might provide a therapeutic tool to treat peripheral demyelinating diseases
    neurologyacquired 
    silencing CDKN1C gene might provide a therapeutic tool to promote myelin restoration after traumatic injury
    ANIMAL & CELL MODELS