Zinc finger BED domain-containing protein 3 also known as axin-interacting protein is a protein in humans that is encoded by the ZBED3 gene.[5]
ZBED3 (Zinc finger BED-type containing 3) is a protein-coding gene arising from hAT DNA transposons[6]. It encodes a 234-amino acid [7] regulatory protein characterized by the presence of a BED-type zinc finger domain, which enables interactions with both DNA and protein partners [8]. ZBED3 is thought to function as a positive regulator of the Wnt/β-catenin signaling pathway, an essential pathway involved in embryonic development [9] and adult stem cell renewal [10]. This regulatory role is mediated through its interaction with the Axin–glycogen synthase kinase 3 beta (GSK3β) complex. By binding to and inhibiting this complex, ZBED3 promotes stabilization of β-catenin, enhancing downstream Wnt signaling activity [11].
The protein contains a conserved PPPPSPT motif that facilitates binding to the Axin–GSK3β complex. Mutations affecting key amino acid residues within this motif have been shown to impair ZBED3’s binding capacity. Experimental knockdown of ZBED3 using RNA interference results in reduced β-catenin levels, potentially affecting signaling pathways [12].
Altered expression of ZBED3 has been associated with several pathological conditions. Reduced expression has been observed kidney renal cell carcinoma [13], while increased expression has been linked to insulin resistance, hyperglycemia [14], and lung cancer [15].
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