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FLASH GENE
Symbol ING1 contributors: mct/npt/pgu - updated : 11-04-2018
HGNC name inhibitor of growth family, member 1
HGNC id 6062
DNA
TYPE functioning gene
STRUCTURE 8.34 kb     2 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status provisional
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
2 - 2861 47 422 minimally expressed 2008 18951897
ING1D
2 - 2887 33 279 adult and fetal tissues, expressed at lower levels 2008 18951897
  • ING1A
  • playing an important role in AFP gene regulation through association with HNF1 and/or AT-motifs
  • enhancing the transcriptional regulatory activity of TP53
  • ING1a tumor suppressor regulates endocytosis to induce cellular senescence via the Rb-E2F pathway
  • 2 - 2131 24 235 can only be detected when overexpressed 2008 18951897
  • ING1C
  • 2 - 2188 - 210 the most highly conserved and the major one expressed in human cells 2008 18951897
  • ING1B
  • interacts with karyopherins alpha2 and beta1 through several basic nuclear localization sequences (NLS) located adjacent to its PHD region
  • its activity is regulated, in part, through dynamic subcellular partitioning between the nucleus and cytoplasm
  • in cancers is mislocalized to the cytoplasm
  • required for the E3 ligase Rad18-mediated PCNA monoubiquitination in lesion bypass
  • upregulates CDKN2A transcription, and its overexpression induces cellular senescence
  • tumor suppressor ING1b binds rDNA, regulates rDNA chromatin modifications and affects nucleolar localization of MTOR to modulate rRNA levels
  • 2 - 1956 - 262 - 2008 18951897
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Lymphoid/Immunespleen   highly
    Reproductivefemale systemovary  highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectivebone   
    cell lineage
    cell lines neuroblastoma cells and other tumor cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • C4-H-C3 PHD zinc finger domain
  • a polybasic region (PBR) adjacent to the PHDs that binds stress-inducible phosphatidylinositol monophosphate (PtIn-MP) signaling lipids to activate ING1
  • HOMOLOGY
    Homologene
    FAMILY
  • ING family
  • CATEGORY regulatory
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,chromatin/chromosome
    intracellular,nucleus,nucleolus
    text localization of ING1 can be modulated by CDKN2A protein levels, causing a displacement from nuclear to nucleolar localization
    basic FUNCTION
  • playing an important role in cellular stress response to ultraviolet radiation (UVR)
  • having apoptotic functions may be exerted by chromatin-related functions that are subject to cell age-dependent mechanisms of regulation
  • involved in the regulation of diverse processes ranging from cell cycle and cellular senescence to apoptosis
  • inducing cell-cycle arrest and apoptosis in a TP53-dependent manner
  • potentially regulate the expression of proteins that are critical for angiogenesis in glioblastoma such as the angiopoietins
  • affect apoptosis, growth, and DNA repair by binding histones and regulating chromatin structure and gene expression
  • critical epigenetic regulator of cellular senescence in human fibroblasts
  • stabilizes TP53 by inhibiting polyubiquitination of multimonoubiquitinated forms via interaction with and colocalization of the USP7-deubiquitinase with TP53
  • ING1-RSL1D1 axis functions as a novel pro-apoptotic regulator in response to DNA damage
  • acts likely at early stages of the DNA damage response activating a variety of repair mechanisms and that this function of ING1 is targeted in tumors.
  • functions as an epigenetic regulator and a type II tumor suppressor
  • role for ING1b SUMOylation in the regulation of gene transcription
  • regulates the nucleolar epigenome and rDNA transcription suggesting that regulation of protein synthesis might serve as the basis for ING1 function as a type II tumor suppressor
  • functional role for the epigenetic regulator ING1 in activity-induced gene expression in primary cortical neurons
  • CELLULAR PROCESS cell life, proliferation/growth
    cell life, cell death/apoptosis
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • stable components of the SIN3A /HDAC and KAT5/NuA4 HAT complexes
  • ING1 and ING2 are stoichiometric members of histone deacetylase complexes
  • INTERACTION
    DNA
    RNA
    small molecule metal binding,
  • Zn2+
  • protein
  • TP53
  • bind PCNA in a DNA damage-dependent manner
  • interact with proteins associated with histone acetyltransferase (HAT) activity, such as TRRAP, PCAF, CBP, and p300
  • binding OEATC1
  • interacting with CDKN2A
  • binds karyopherin proteins and disruption of this interaction affects cell localization and ING activity as a transcriptional regulator
  • physically interacts with herpesvirus-associated ubiquitin-specific protease (USP7), a TP53 and MDM2 deubiquitinase (DUB)
  • ING1 is a binding partner that interacts with RSL1D1 (after UV irradiation, ING1 increases its protein expression, translocates into the nucleolus and binds RSL1D1)
  • ITSN2 is a major transducer of ING1a-induced senescence signaling
  • SRC antagonizes the ability of ING1 to induce apoptosis, most likely through relocalization of ING1 and down regulation of ING1 levels
  • ING1 interacts with the proliferating cell nuclear antigen (PCNA) in a UV-inducible manner
  • endogenous ING1 protein specifically interacts with the pro-apoptotic BCL2 family member BAX, and colocalizes with BAX in a UV-inducible manner
  • potential crosstalk between ING1 and ING2 tumor suppressors to inhibit AR signaling and induce cellular senescence in PCa cells
  • cell & other
    REGULATION
    induced by UV irradiation
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    in breast cancer
    tumoral   LOH    
    or loss of function in head and neck squamous cell carcinomas
    tumoral     --over  
    in melanoma cell lines
    tumoral   deletion    
    or mutation in melanoma with poor prognosis
    tumoral     --over  
    in stromal cells can promote the development of breast cancer through increased expression and release of MMPs and down regulation of TIMPs
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS