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Identification of a functional nuclear localization signal mediating nuclear import of the zinc finger transcription factor ZNF24. | LitMetric

AI Article Synopsis

  • ZNF24 is a zinc finger transcription factor crucial for cell growth and differentiation, with its method of nuclear entry still not fully understood.
  • Researchers identified that the nuclear localization signal (NLS) is located within the first two zinc finger domains (ZF1-2) of ZNF24, which are necessary for its movement into the nucleus.
  • Mutations affecting the structure of ZF1 or ZF2 don't prevent nuclear localization, but certain mutations do lead to cytoplasmic accumulation, indicating that ZF1-2 is essential for ZNF24's nuclear function and its ability to activate gene expression.

Article Abstract

ZNF24 is a member of the SCAN domain family of Krüppel-like zinc finger (ZF) transcription factors, which plays a critical role in cell proliferation and differentiation. However, how ZNF24 enters the nucleus in order to exert its function remains unclear since its nuclear localization signal(s) (NLS) has not been identified. Here, we generated a series of GFP-tagged deletion and point mutants and assessed their subcellular localization. Our results delimit the NLS to ZF1-2. Deletion of ZF1-2 caused cytoplasmic accumulation of ZNF24. Fusion of the ZF1-2 to green fluorescent protein (GFP) targeted GFP to the nucleus, demonstrating that the ZF1-2 is both necessary and sufficient for nuclear localization. ZNF24 containing histidine to leucine mutations that disrupt the structure of ZF1 or/and ZF2 retains appropriate nuclear localization, indicating that neither the tertiary structure of the zinc fingers nor specific DNA binding are necessary for nuclear localization. K286A and R290A mutation led to partial cytoplasmic accumulation. Co-immunoprecipitation demonstrated that ZNF24 interacted with importin-β and this interaction required the ZF motifs. The β-Catenin (CTNNB1) luciferase assays showed that the ZNF24 mutants defective in nuclear localization could not promote CTNNB1 promoter activation as the wild-type ZNF24 did. Taken together, these results suggest that consecutive ZF1-2 is critical for the regulation of ZNF24 nuclear localization and its transactivation function.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3815127PMC
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0079910PLOS

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