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FLASH GENE
Symbol PSMD10 contributors: mct - updated : 07-02-2018
HGNC name proteasome (prosome, macropain) 26S subunit, non-ATPase, 10
HGNC id 9555
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • N terminus which contains the nuclear export sequence (NES), is responsible for suppressing NF-kappaB/RelA nuclear translocation (Chen 2008)
  • seven ANK repeats, required for the interaction with RELA
  • CDK4-binding site and Rb-binding site located in N- and C-terminal regions, respectively
  • HOMOLOGY
    interspecies homolog to murine PSMD10
    Homologene
    FAMILY
    CATEGORY chaperone/stress , regulatory , protooncogene
    SUBCELLULAR LOCALIZATION extracellular
        intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,nucleoplasm
    basic FUNCTION
  • acting as a regulatory subunit of the 26s proteasome which is involved in the ATP-dependent degradation of ubiquitinated proteins
  • playing an important role in the development of hepatocellular carcinomas
  • ankyrin repeat anti-apoptotic oncoprotein that is commonly overexpressed in hepatocellular carcinomas and increases the degradation of TP53 and Rb (Chen 2008)
  • during ER stress, p28(GANK) enhances the unfolded protein response, promotes ER recovery from translational repression, and thereby facilitates cell's ability to cope with the stress conditions
  • is a key regulator of RAS-mediated activation of AKT1 through inhibition of the downstream RHOA/ROCK pathway and thus plays an essential role in RAS-induced tumorigenesis
  • chaperone of ubiquitin-proteasome, having an essential role in breast cancer metastasis
  • is crucial for breast cancer metastasis
  • is a regulator of cellular redox homeostasis, providing a link between oxidative stress and the development of hepatocellular carcinoma
  • may exert a pro-oncogenic function in the prostate
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • CDK4, PSMC4
  • directly binds to NF-kappaB/RELA and exports RELA from nucleus through a chromosomal region maintenance-1 (CRM1) dependent pathway, which results in the cytoplasmic retention of NF-kappaB/RELA (Chen 2008)
  • PSMD10 expression is regulated by a positive feedback loop involving CTNNB1, which may play a critical role in tumorigenesis and the progression of Hepatocellular carcinoma P
  • CDH1 was found to be involved in the PSMD10 induced invasion of breast cancer cells due to hypoxia
  • PSMD10 was physically associated with ATG7 in the cytoplasm, and this association was enhanced by initial nutrient deprivation
  • oncoprotein that facilitates the degradation of two key tumor suppressors, namely, RB1 and TP53
  • interact with the Kelch domain of KEAP1 and effectively competed with NFE2L2 for KEAP1 binding
  • involved in the inhibition of differentiation of hepatic stem cells (HSC) via triggering degradation of tumor suppressor proteins RB1, TP53, CEBPA and HNF4A
  • CELF1 is both a tumor suppressor and target of PSMD10-mediated degradation when unphosphorylated at Ser302
  • PSMD10-mediated reduction of CELF1 is critical for the development of hepatoblastoma (HBL)
  • PSMD10 is a novel downstream effector of KDM4A
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in hepatocellular carcinoma contributing to the metastasis potential in the process of carcinogenesis
    tumoral     --over  
    in hepatocellular carcinoma cells blocked the binding between NFE2L2 and KEAP1, inhibiting the degradation of NFE2L2 by proteasome
    tumoral     --over  
    in gastric cancer compared to non-cancerous tissues
    tumoral   deletion    
    abrogated the increased metastatic potential of breast cancer cells under hypoxic conditions partly through regulating CDH1
    tumoral     --over  
    associated with extensive intraductal carcinoma and ERBB2 expression in breast cancer
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerdigestiveoesophagus
    could be a potential effective therapeutic target for enhancing chemosensitivity to 5-fluorouracil and cisplatin
    cancerdigestiveliver
    Targeting of PSMD10 might therefore be an attractive strategy in HCC treatment by suppressing autophagy and inducing HCC cell sensitivity to drugs
    cancerreproductivebreast
    potential of PSMD10 as a therapeutic target for tumor metastasis
    ANIMAL & CELL MODELS