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FLASH GENE
Symbol TP73 contributors: mct/npt/pgu - updated : 18-06-2015
HGNC name tumor protein p73
HGNC id 12003
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • N-terminal transactivation domain with strong homology to the core DNA binding region of TP53
  • DNA binding and tetramerization domains
  • C-terminal SAM domains, sterile alpha motif, SAMp73, involved in lipid binding and it is thought to mediate in protein-protein interactions
  • HOMOLOGY
    intraspecies homolog to TP53
    Homologene
    FAMILY
  • TP53 family
  • CATEGORY transcription factor , tumor suppressor
    SUBCELLULAR LOCALIZATION     plasma membrane,junction
        intracellular
    intracellular,cytoplasm,organelle,Golgi
    intracellular,nucleus,nucleoplasm
    intracellular,nucleus,chromatin/chromosome
    basic FUNCTION
  • activating transcription of TP53-responsive genes and inhibiting cell growth by inducing apoptosis
  • putatively involved in neurogenesis sensory pathways and homeostatic control judging from TP73-deficient mice
  • with ZNF143 and its target genes, involved in DNA repair gene expression and cisplatin resistance
  • displaying a tumor suppressor activity similar to TP53
  • regulator of SAC responses and TP73 loss can lead to mitotic arrest defects
  • play a role in erythroid differentiation and may have a physiological role in developmental erythropoiesis
  • role for TP73 and CKAP4 in supporting cellular proliferation through the transcriptional activation of the genes involved in G(1)-S and G(2)-M progression
  • has a role in macrophage polarization and innate immunity, enhancing the action field of this important regulatory molecule
  • plays a critical role in tumor suppression and neural development
  • is a critical downstream mediator of HDAC1-regulated cell migration
  • mutual regulation between TP73 and TRIM32 constitutes a novel feedback loop, which might have important implications in central nervous system development as well as relevance in oncogenesis
  • has a unique role in spermatogenesis that ensures the maintenance of mitotic cells and normal spermiogenesis
  • TP73 is essential for germ cell adhesion and maturation in testis
  • can induce cell cycle arrest or apoptosis by the activation of TP53-responsive genes as well as TP53-independent pathways
  • TP73 was required for TP53 stabilization and accumulation under AMPK activation, but was dispensable under DNA damage
  • function as a tumor suppressor and regulates genomic integrity, cellular proliferation, and apoptosis
  • is a novel central regulator of Motile multiciliated cells (MCCs) differentiation
  • CELLULAR PROCESS nucleotide, transcription
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • RANBP9/TP73 complex implicated in mitochondria-mediated apoptosis in addition to its role in enhancing APP generation
  • INTERACTION
    DNA DNA binding
    RNA
    small molecule
    protein
  • directly interacts with Sp1, suggesting that formation of a TP73-Sp1 complex is the underlying mechanism for TP73-triggered inhibition of TERT expression
  • interacting with HCK (HCK-SH3 domain-mediated interactions play an important role in the inhibition of TP73-dependent transcriptional activation of a target gene, NLRC4, as well as apoptosis)
  • interact directly with several partners of the SAC, spindle assembly checkpoint, complex (BUB1, BUB3, and BUB1B)(involved in SAC protein localization and activities)
  • interacting with ZNF143
  • interacting with SHISA5 (induces ER stress via the direct transactivation of Scotin)
  • interacts with CGTHBA (can modulate differentially the specific activities of selected TP73 isoforms)
  • TP73 binds to CASP8AP2 and is part of the complex that regulates histone gene transcription
  • ubiquitination of TP73 mediated by RCHY1 represents an important pathway for controlling the suppressive function of TP73
  • RBM38 is a target of TP73, the mutual regulation between TP73 and RBM38 constitutes a novel feed-forward loop, which might be explored as a target for tumors without a functional TP53
  • important role of deregulated E2F in activation of the TP73 gene, a component of major intrinsic tumor suppressor pathways
  • RANBP9 and TP73 have cooperative roles in inducing cell death, and the RANBP9/TP73 complex is implicated in mitochondria-mediated apoptosis in addition to its role in enhancing APP generation
  • HDAC1 is a key regulator of TP73 protein stability
  • TRIM32, a new direct TP73 transcriptional target in the context of neural progenitor cells, is differentially regulated by TP73
  • TP73 regulates GLS2 during retinoic acid-induced terminal neuronal differentiation of neuroblastoma cells
  • WWP2, an E3 ligase, is a novel TP73-associated protein that ubiquitinates and degrades TP73
  • functional E3 ligase complex controlled by PPM1G that differentially regulates cellular TP73 and deltaNp73
  • RPL11 and RPL5 activate TP73 by overcoming MDM2 inhibition
  • TP73 directly activates the key regulators FOXJ1, RFX2, RFX3
  • cell & other
    REGULATION
    activated by RPL11 and RPL5 that activate TP73 by overcoming MDM2 inhibition
    induced by E2F1 for apoptosis
    Other regulation of TP73 by the Cullin4A (cul4A)-dependent ligase (CDL4A) E3 complex, through the inhibition of its transcriptional function
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in bladder carcinoma
    tumoral   deletion    
    in neuroblastoma in advanced stage
    tumoral   amplification    
    in neuroblastoma,primary sqamous, primary sqamous cell carcinoma of the lung, head and neck cancer cell line
    tumoral   LOH    
    in hepatocellular carcinoma
    tumoral       loss of function
    by abnormal methylation or LOH in non-Hodgkin lymphoma
    tumoral     --low  
    correlates with increases of SAC protein expression in patients with lung cancer
    tumoral     --low gain of function
    loss of TAp73 or deltaNp73 up-regulation activates the angiogenic switch that stimulates tumor growth and progression
    tumoral     --low  
    TP73 methylation is common in patients with myelodysplastic syndromes and is associated with poor prognosis
    Susceptibility to cancer
    Variant & Polymorphism SNP
  • polymorphism (G4C14-A4T14) probably associates with cancer risk
  • Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • Tp73 is a transcriptional activator of Ngfr and Ngfr mRNA and protein levels are strongly reduced in the central and peripheral nervous systems of p73 knockout mice