Disease relevance of Pcbp1

• RESULTS: When compared to dams fed a folate-replete diet, those dams on a folate-depleted diet developed reduced red cell folates and hyperhomocysteinemia and an inverse dose-dependent upregulation of FR and hnRNP-E1 on GD17 without alterations in cell number in the majority of tissues [1].

High impact information on Pcbp1

• Detection of this "alpha-complex" has been limited to in vitro studies, and the functional state of the alpha-globin mRNA targeted by alphaCP has not been defined [2].
• PABP inhibited ErEN activity indirectly through an interaction with the alphaCP mRNA stability protein [3].
• Sequestration of alphaCP resulted in an increase of ErEN cleavage activity, regardless of the polyadenylation state of the RNA [3].
• Interestingly, the binding domain of one of the CCAAT factors, alpha-CP1, overlapped one alpha-IRP binding site. alpha-CP1 thus overlapped the binding domains of both alpha-CP2 and alpha-IRP [4].
• In contrast, when sedimented in glycerol gradients containing 500 mM KCl, alpha-CP1 dissociated into at least two components [5].

Biological context of Pcbp1

• The alphaCP-1 and alphaCP-2 genes were shown to be single copy and were mapped to separate chromosomes [6].
• The stringent structural conservation of alphaCP-1 and its ubiquitous tissue distribution suggested that the retrotransposed alphaCP-1 gene was rapidly recruited to a function critical to the cell and distinct from that of its alphaCP-2 progenitor [6].
• The binding sites of two proteins, termed alpha-CP1 and alpha-CP2, overlapped in the CCAAT box [4].
• We have used DNA sequence affinity chromatography previously to purify a murine erythroid cell nuclear factor termed alpha-CP1 [7].
• CONCLUSIONS: Maternal folate deficiency results in selective upregulation of FR and hnRNP-E1 associated with multiple aberrations in fetal tissues that include increased cell loss, architectural anomalies, and premature differentiation [1].

Anatomical context of Pcbp1

• This study examines the role of alphaCP in the decay of transcripts containing the collagen 3'-UTR in extracts obtained from NIH fibroblasts and quiescent and activated HSCs [8].
• Fetuses from some groups were evaluated by specific biochemical, molecular, and immunohistochemical studies for FR, hnRNP-E1, and apoptosis [1].

Physical interactions of Pcbp1

• Affinity purification of NF-M 3'-UTR-binding proteins from rat brain followed by mass spectrometry and immunoprecipitation assays identified heterogeneous nuclear ribonucleoprotein (hnRNP) K and hnRNP E1 as the proteins forming the 70- and 47-kDa complexes, respectively [9].
• Targeted analysis of the polysomal RNP complexes revealed that alphaCP is specifically bound to actively translating alpha-globin mRNA [2].

Regulatory relationships of Pcbp1

• In contrast protease treatment abolishes the ability of alpha-CP1 to activate alpha-globin gene transcription in vitro [7].

Other interactions of Pcbp1

• These data suggested that the alphaCP-1 gene was generated by retrotransposition of a fully processed alphaCP-2 mRNA and that this event occurred well before the mammalian radiation [6].
• Two of the purified proteins, alpha-CP1 and alpha-CP2, have been shown previously to interact with distinct binding sites that overlap in the alpha-globin CCAAT box [5].
• Since hnRNP E is known to stabilize mRNAs, these results raise the hypothesis that these proteins may contribute to the increases in cytoplasmic levels of NF-M mRNA that accompany axonal maturation [9].

Analytical, diagnostic and therapeutic context of Pcbp1

• In addition chemical cross-linking, sedimentation, and gel filtration studies suggest that alpha-CP1 is a heterotrimeric factor composed of one polypeptide from each class [7].

References