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FLASH GENE
Symbol CPSF4 contributors: mct - updated : 23-03-2020
HGNC name cleavage and polyadenylation specific factor 4, 30kDa
HGNC id 2327
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a RNA-binding zinc finger protein, with five Cys3His domains (annotated as "zinc-finger" domains, that is a critical determinant of specific AAUAAA motif recognition
  • mono polymer complex
    HOMOLOGY
    Homologene
    FAMILY
    CATEGORY enzyme , RNA associated
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,nucleoplasm
    basic FUNCTION
  • component of the cleavage and polyadenylation specificity factor (CPSF) complex that play a key role in pre-mRNA 3'-end formation
  • CPSF4 and its homologues are likely the actual nucleases that cleave pre-mRNA in the process of polyadenylation
  • plays a key role in mRNA polyadenylation and mRNA 3' ends maturation
  • plays a critical role in regulating lung cancer cell proliferation and survival
  • CPSF4 and WDR33 directly contact AAUAAA
  • key protein involved in pre-mRNA processing
  • CPSF1 functions as an essential scaffold and preorganizes CPSF4 and WDR33 for high-affinity binding to AAUAAA
  • selectively recognizes the AU-rich hexamer (AAUAAA) sequence present in pre-mRNA, providing the first molecular-based evidence to our knowledge for CPSF4/RNA binding
  • crucial tumorigenic factor in lung cancer development
  • both CPSF4 and WDR33 are required for high-affinity binding of the AAUAAA polyadenylation signal (PAS) RNA, while these two proteins alone and their binary complexes with CPSF1 have much lower affinity for the RNA
  • CELLULAR PROCESS nucleotide, transcription, maturation
    protein, translation/synthesis
    PHYSIOLOGICAL PROCESS
    text polyadenylation
    PATHWAY
    metabolism
    signaling
  • role of the CPSF4/PTGS2 signaling pathway in the regulation of lung cancer growth and progression
  • a component
  • complexing with CPSF1, 2, 3 poly (A) ribonuclease (PARN) and CSTF3 (cleavage stimulation factor 3)
  • a core CPSF complex comprising CPSF1, WDR33, CPSF4 and FIP1L1 is sufficient for AAUAAA motif recognition, necessary for 3' polyadenylation, a key step in eukaryotic mRNA biogenesis
  • INTERACTION
    DNA
    RNA binding to the AAUAA motif of the pre mRNA, upstream the cleavage site
    small molecule
    protein
  • associate with some other CPSF subunits
  • NS1A proteins of human influenza A viruses bind CPSF4, a cellular factor required for the processing of cellular pre-mRNAs, thereby inhibiting the production of all cellular mRNAs, including beta interferon mRNA(pMID: 17522219)
  • CPSF4 plays a critical role in the regulation of TERT expression and lung tumorigenesis and may be a new prognosis factor in lung adenocarcinomas
  • CREBBP regulates lung cancer growth by targeting MAPK and CPSF4 signaling pathways 8)
  • CPSF4 bind to PTGS2 promoter sequences directly and activate the transcription of PTGS2
  • CPSF4 facilitated colorectal tumorigenesis and development partially through transcriptionally regulating TERT expression by cooperating with NFKB1 and co-anchoring at TERT promoter -321 to -234 fragment
  • cell & other
    REGULATION
    inhibited by influenza virus NS1 protein
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in human colon cancer cells and tissues
    tumoral     --over  
    in lung adenocarcinoma cell lines and tumor tissue (pMID: 24358221)
    tumoral     --over  
    of CPSF4 and PTGS2 proteins predicted poor prognosis of patients with lung cancers
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • may be a potential prognostic biomarker for lung adenocarcinoma
  • Therapy target
    SystemTypeDisorderPubmed
    cancerdigestivecolon
    targeting CPSF4-TERT axis may represent a promising therapeutic strategy in colon cancer treatment
    cancerlung 
    potential therapeutic target for lung adenocarcinoma
    ANIMAL & CELL MODELS