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FLASH GENE
Symbol CDKN1A contributors: npt/mct - updated : 20-09-2017
HGNC name cyclin-dependent kinase inhibitor 1A (p21, Cip1)
HGNC id 1784
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Cardiovascularheart   moderately
Digestivemouth   moderately
 salivary gland   moderately
 stomach   highly
Endocrinepancreas   moderately
Hearing/Equilibriumearinnercochlea highly
Lymphoid/Immunethymus   moderately
Nervousnerve   highly
Reproductivefemale systemuteruscervix moderately
Respiratorylung   predominantly
Skin/Tegumentskin   highly
Visualeye   moderately
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Connectiveadipose  highly
Lymphoid    
cell lineage
cell lines
fluid/secretion
at STAGE
physiological period embryo
cell cycle     cell cycle, interphase, G1
Text embryonic tissue
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • N-terminal region required for repression of gene expression of CCNE2 and other genes
  • a CDK inhibitory domain
  • a proline-rich domain
  • an acidic repeat region
  • a conserved C terminal domain hybridizing with WI-7311, WI-10190
  • HOMOLOGY
    interspecies homolog to rattus Cdkn1a (76.54 pc)
    homolog to murine Cdkn1a (79.25 pc)
    Homologene
    FAMILY
  • CDK inhibitor family
  • CATEGORY enzyme , regulatory
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,nucleoplasm
    text apoptosis
    basic FUNCTION
  • wild type p53-activated fragment 1 mediating the cell cycle G1 phase arrest in response of various stress stimuli
  • involved in an age-dependent increase in cell cycle negative regulation of the Human Corneal Endothelial Cells (HCEC)
  • may be responsible, at least in part, for the reduced proliferative response observed in HCECs from older donors
  • upstream regulator of DNMT1 expression, and negatively regulates DNMT1 expression in mammalian cells
  • major cell cycle regulator of the response to DNA damage, senescence and tumor suppression
  • plays an essential role in promoting cell cycle exit in endocrine progenitors downstream of NEUROG3)
  • exerts a repressive effect on a relevant number of genes controlling S phase and mitosis
  • is a crucial downstream effector of TRIM39 mediating G1/S transition and DNA damage-induced G2 arrest
  • is necessary for proper control of the cell cycle and premature senescence
  • CELLULAR PROCESS cell cycle
    PHYSIOLOGICAL PROCESS development
    text
  • CDK inhibitor controlling differentiation of skeletal muscle and alveoli in the lung in parallel with P21 and myogenin
  • suppressor of malignant skin tumor formation and as a determinant of keratinocyte stem-cell potential
  • regulator at G1 cell cylce exit in megacaryocytes
  • PATHWAY
    metabolism
    signaling
    CDKN1A-EP300-DNMT1 pathway may play a pivotal role to ensure regulated DNMT1 expression and DNA methylation in mammalian cell division
    a component
  • CDKN1A/NFYA/PLK1 axis critical for maintaining the checkpoint function of TP53 to prevent mitotic death in the DNA damage-induced response
  • KDM8/CDKN1A (p21) axis is essential to maintaining the short G1 phase which is critical for pluripotency in hESCs
  • FUBP1-FUSE complex is an essential component of a transcription molecular machinery that is necessary for tight regulation of expression of many key genes including MYC and CDKN1A
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • TYMS
  • inhibiting CDK2, CDK4 complexes
  • inhibiting cycle progression by interacting with G1 cyclin/CDK complexes and PCNA
  • CCNE2
  • PBK interacts with the DBD domain of tumor suppressor TP53 and modulates expression of transcriptional targets including CDKN1A
  • TFAP2A binds CDKN1A to two regions of the promoter: the proximal region where the AP-2 site lies and upstream near the major TP53 binding site
  • SSBP1 directly binds CDKN1A and this interaction may prevent CDKN1A from ubiquitin-mediated degradation
  • SNW1-associated factors DHX8 and PRPF19 are also selectively required for CDKN1A expression under stress
  • new function of SRSF2 in the process of cellular senescence and CDKN1A is a key target of SRSF2 in this setting
  • acted in part to mediate growth suppression by ARID1A
  • cooperative and interdependent roles for ARID3A and TP53 in the transcriptional activation of CDKN1A in response to DNA damage
  • KDM8 physiologically moderates embryonic cell proliferation through the epigenetic control of CDKN1A expression
  • RNF144B is a potentially critical component of epithelial homeostasis, acting downstream of TP63 to regulate cellular levels of CDKN1A and TP63
  • HIC1 is a direct transcriptional repressor of CDKN1A and is a key player in the regulation of the DNA damage response
  • KAT5-mediated CDKN1A acetylation is a novel and essential regulatory process required for CDKN1A-dependent DNA damage-induced cell-cycle arrest
  • Aurora B represses CDKN1A, preventing delayed DNA replication, CDK inhibition and premature mitotic exit
  • UCHL5 is also required for high glucose-induced TGFBR1 protein deubiquitination, CDKN1A and fibronectin protein expression and cell hypertrophy
  • RNF114 activates cell cycle progression and suppresses cellular senescence through the RING domain-mediated degradation of CDKN1A
  • unexpected role of MAPK14 in cell cycle regulation in response to Aurora B inhibition, by promoting the transcriptional elongation of the cell cycle inhibitor CDKN1A
  • FMN2 is a crucial protein involved in the control of CDKN1A (
  • CDKN2A stabilizes the CDKN1A mRNA through negative regulation of the mRNA decay-promoting HNRNPD protein
  • has dual effects under HSPA9-depleted conditions, i.e., mediating cell cycle arrest while limiting cell death
  • transcriptional repression of BMP2 by CDKN1A links quiescence to neural stem cell maintenance
  • TSG101 protein interacts with and down-regulates the promoter of CDKN1A tumor suppressor gene
  • TAF1 is able to phosphorylate TP53 on Thr55, which leads to dissociation of TP53 from the CDKN1A promoter
  • RBM24 is a target gene of the TP53 protein, and can regulate CDKN1A expression via mRNA stability
  • TOP3A binds to the TP53 and CDKN1A promoters and positively regulates their expression, contributing to the TP53-mediated tumor suppression
  • DUX4 might potentially induce proliferation inhibition and G1 phase arrest through upregulation of CDKN1A
  • RASSF6 triggers CDKN1A accumulation to induce G 1 cell cycle arrest and promote apoptosis upon exposure to pro-apoptotic agents
  • TWIST2 directly regulated CDKN1A in hematopoietic cells and whose silence promoted cell proliferation and cell cycle progression, this direct regulation of CDKN1A by TWIST2 has a role in its tumor-suppressor function in AML (acute myeloid leukemia)
  • CDKN1A/CCNE1 pathway is crucial in modulating the anticlastogenic function of BMI1
  • NR5A2 cooperates with FOXA1 and binds directly to CDKN1A promoter and a distal regulatory region found at -62&
  • 8201;kb from its transcriptional start sites, allowing repression of CDKN1A transcription
  • ANKHD1 promotes Multiple myeloma growth by repressing CDKN1A a potent cell cycle regulator
  • MORC2 down-regulated CDKN1A by recruiting HDAC1 to the CDKN1A promoter, in a TP53-independent manner
  • TGM2-mediated autophagy and CDKN1A-mediated cell cycle arrest are two important barriers in the TP53 pathway that prevent oncogenic transformation
  • CDKN1A repression by TBX3 is biologically significant and required for TBX3-induced cell proliferation of chondrosarcoma cells
  • ASPSCR1-TFE3 fusion protein regulates cell cycle progression and induces cellular senescence by up-regulating CDKN1A expression
  • MELK is an interacting partner of CDKN1A (interaction through the cyclin-dependent kinase (CDK) binding region of CDKN1A and the C-terminal domain of MELK)
  • NFIC may contribute to postnatal chondrocyte proliferation by inhibiting CDKN1A expression and by increasing the stability of CCND1 protein
  • CCN3 may in part promote chondrocyte senescence, leading to the degeneration of articular cartilage through the induction of TP53 and CDKN1A
  • cell & other
    REGULATION
    activated by TP53
    KLF1 (directly activates CDKN1A by proximal promoter and novel intronic regulatory regions during erythroid differentiation)
    induced by chimeric oncoprotein SS18-SSX1 for suppression of cell growth
    low concentration of Cl-
    inhibited by AMPHL in early stage of muscle differentiation program
    repressed by TYMS
    ZBTB2 by a direct interaction with TP53 and SP1
    Phosphorylated by PIM2, that phosphorylates CDKN1A on Thr145
    Other cleaved by caspase 3 in the earlier stage of apoptosis
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral        
    papillary thyroid carcinoma
    tumoral     --low  
    in adult T-cell leukemia/lymphoma (ATLL) cells may be a key player in ATLL leukemogenesis, and the abnormal genomic methylation may influence the expression of not only HTLV-1 TAX but also CDKN1A during long-term development of ATLL from the HTLV-1-infected T lymphocytes
    Susceptibility
  • esophageal cancer, cervical cancer
  • to advanced prostate carcinoma
  • to colorectal cancer
  • Variant & Polymorphism other
  • variant of the codon 31 increasing in primary cervical cancer (Japanese)
  • genotype CT and TT strongly associated with advanced prostate carcinoma
  • rs1321311, near CDKN1A influences colorectal cancer risk
  • Candidate gene
    Marker
  • cell free plasma expressions of CDKN1A and HIF1A were more prevalent in pregnancies complicated by hypoxia and/or IUGR
  • Therapy target
  • being a novel, unique therapeutic strategy for gastric cancer treatment via control of decreased the intracellular chloride concentration
  • ANIMAL & CELL MODELS