Disease relevance of Pabpc1

• We report that infection of MT-2 cells with HIV-1 leads to efficient proteolysis of PABP [1].
• Cleavage of PABP by viral proteases encoded by several picornaviruses and caliciviruses plays a role in the abrogation of cellular protein synthesis [1].
• Purified HIV-1 and HIV-2 proteases cleave PABP1 directly at positions 237 and 477, separating the two first RNA-recognition motifs from the C-terminal domain of PABP [1].
• HIV protease cleaves poly(A)-binding protein [1].
• These findings indicate that some retroviruses may share with picornaviruses and caliciviruses the capacity to proteolyse PABP [1].

High impact information on Pabpc1

• We recently identified an embryonic poly(A)-binding protein (ePAB) in Xenopus. ePAB is the predominant cytoplasmic PABP in Xenopus oocytes and early embryos and prevents deadenylation of mRNAs, suggesting its importance in the regulation of gene expression during early Xenopus development [2].
• An embryonic poly(A)-binding protein (ePAB) is expressed in mouse oocytes and early preimplantation embryos [2].
• However, the cytoplasmic somatic cell poly(A)-binding protein (PABP1) is not expressed until later in embryogenesis [2].
• The methylation of two known CARM1 substrates, poly(A)-binding protein (PABP1) and the transcriptional cofactor p300, was abolished in knockout embryos and cells [3].
• Embryonic poly(A)-binding protein stimulates translation in germ cells [4].

Biological context of Pabpc1

• Second, mRNAs encoding somatic PABP isoform, PABP1, are present at high levels in meiotic and haploid spermatogenic cells [5].
• This synergy is mediated via interactions between eIF4G (a component of the eIF4F cap binding complex) and poly(A) binding protein (PABP) [6].
• Although inducers do not alter initiation factor modifications, characterization of their effect on mRNA translation provides evidence that this is mediated by the poly(A)-binding protein (PABP) [7].
• The role of eIF4G during the initiation of protein synthesis was studied using mouse mammary carcinoma FM3A cells and FM4G cells that overproduce an N-terminally truncated form of eIF4G, which lacks the binding site of poly(A)-binding protein [8].

Anatomical context of Pabpc1

• Most of the PABP1 message accumulated by growing oocytes decays during meiotic maturation with transcription resuming in two-cell embryos [9].
• Three cDNAs encode for smooth muscle actin, one for fibronectin and one for polyadenylate binding protein [10].
• These data suggest that the PABP plays a role in the accumulation of these 80 S ribosomal.mRNA complexes and may facilitate the formation of translationally active salt-stable ribosomes [7].
• Immunoblotting demonstrates that the mRNAs in these 80 S ribosomal complexes do not contain bound PABP and that this protein is found to be almost exclusively associated with translating polysomes [7].

Other interactions of Pabpc1

• First, the promoter of the Pabp2 gene is not derived from its intron-containing progenitor, Pabp1 [5].
• The mRNA for poly(A)-binding protein behaved similarly to EF-1 alpha [11].

Analytical, diagnostic and therapeutic context of Pabpc1

• In the immunoprecipitation analysis, the poly(A)-binding protein (PABP) and the RNA-binding protein HuR were pulled down by 3'-UTR cRNA, and the absence of the ARE site reduced the binding of these proteins [12].

References