title: Each member of the poly-r(C)-binding protein 1 (PCBP) family exhibits iron chaperone activity toward ferritin.
abstract: The mechanisms through which iron-dependent enzymes receive their metal cofactors are largely unknown. Poly r(C)-binding protein 1 (PCBP1) is an iron chaperone for ferritin; both PCBP1 and its paralog PCBP2 are required for iron delivery to the prolyl hydroxylase that regulates HIF1. Here we show that PCBP2 is also an iron chaperone for ferritin. Co-expression of PCBP2 and human ferritins in yeast activated the iron deficiency response and increased iron deposition into ferritin. Depletion of PCBP2 in Huh7 cells diminished iron incorporation into ferritin. Both PCBP1 and PCBP2 were co-immunoprecipitated with ferritin in HEK293 cells, and expression of both PCBPs was required for ferritin complex formation in cells. PCBP1 and -2 exhibited high affinity binding to ferritin in vitro. Mammalian genomes encode 4 PCBPs, including the minimally expressed PCBPs 3 and 4. Expression of PCBP3 and -4 in yeast activated the iron deficiency response, but only PCBP3 exhibited strong interactions with ferritin. Expression of PCBP1 and ferritin in an iron-sensitive, ccc1 yeast strain intensified the toxic effects of iron, whereas expression of PCBP4 protected the cells from iron toxicity. Thus, PCBP1 and -2 form a complex for iron delivery to ferritin, and all PCBPs may share iron chaperone activity.
authors: From the Liver Diseases Branch, NIDDK, National Institutes of Health, Bethesda, Maryland 20892-1800, USA.
authors: Sebastien
authors: S
authors: Leidgens
authors: Kimberly Z
authors: KZ
authors: Bullough
authors: Haifeng
authors: H
authors: Shi
authors: Fengmin
authors: F
authors: Li
authors: Minoo
authors: M
authors: Shakoury-Elizeh
authors: Toshiki
authors: T
authors: Yabe
authors: Poorna
authors: P
authors: Subramanian
authors: Emory
authors: E
authors: Hsu
authors: Navin
authors: N
authors: Natarajan
authors: Anjali
authors: A
authors: Nandal
authors: Timothy L
authors: TL
authors: Stemmler
authors: Caroline C
authors: CC
authors: Philpott
mesh_terms: D002460:Cell Line; D004268:DNA-Binding Proteins; D005293:Ferritins / Q000737:chemistry / Q000378:metabolism*; D015870:Gene Expression; D017930:Genes, Reporter; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000096:biosynthesis / Q000737:chemistry / Q000502:physiology*; D006801:Humans; D047468:Immunoprecipitation; D007501:Iron / Q000378:metabolism*; D009841:Oligonucleotides / Q000737:chemistry; D011485:Protein Binding; D016601:RNA-Binding Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000502:physiology*; D011994:Recombinant Proteins / Q000096:biosynthesis; D012441:Saccharomyces cerevisiae / Q000254:growth & development / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
chemical_list: C090297:AFT1 protein, S cerevisiae; D004268:DNA-Binding Proteins; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D009841:Oligonucleotides; C094604:PCBP1 protein, human; C501903:PCBP2 protein, human; C547062:PCBP3 protein, human; C411734:PCBP4 protein, human; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D005293:Ferritins; D007501:Iron
keywords: Iron; Metals; Molecular Chaperone; Ribonuclear Protein (RNP); Transport Metals; Yeast Metabolism; hnRNP
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