Polyadenylate-binding protein cytoplasmic 1 (PABPC1) (PABPC1)

Polyadenylate-binding protein cytoplasmic 1 (PABPC1) is a vital RNA-binding protein that specifically interacts with the 3' poly(A) tail of eukaryotic mRNAs [UniProt P11940]. It serves as a scaffold for the assembly of the translation initiation complex by binding to the initiation factor eIF4G, which leads to mRNA circularization and efficient ribosome recruitment [Kuo et al., 2019]. In various malignancies, PABPC1 is frequently upregulated and participates in the formation of tumor-specific ribonucleoprotein (RNP) complexes that selectively enhance the translation of mRNAs encoding pro-survival and proliferative factors [Zhang et al., 2021]. These complexes are increasingly recognized as potential therapeutic targets because their disruption can specifically inhibit the oncogenic protein synthesis program [Wang et al., 2020]. Current drug discovery efforts are focused on identifying small molecules or antisense agents that can interfere with PABPC1's ability to bind RNA or its protein partners [PubMed: 29153491]. However, a significant hurdle in targeting PABPC1 is its essential role in normal cellular homeostasis, necessitating strategies that can distinguish between physiological and tumor-specific RNP assemblies to minimize systemic toxicity [Zhang et al., 2021].

Other names

PABP1PABP-1PAB1Poly(A)-binding protein 1Tumor-specific ribonucleoprotein complex containing PABP1

Disruption of the PABPC1-eIF4G interaction or PABPC1-poly(A) binding to inhibit oncogenic mRNA translation and stability.