Identification of a polypeptide sequence that mediates nuclear localization of the acute phase protein C-reactive protein.
C-reactive protein (CRP) is the prototypic human acute phase serum protein. CRP binds to several nuclear Ag including chromatin, histones, and small nuclear ribonucleoproteins. Binding to sites of tissue inflammation and the nuclei of inflammatory cells has been demonstrated in vivo. We also noticed significant similarity between CRP and nucleoplasmin, a molecule with nuclear localization activity. We therefore decided to test whether CRP was capable of nuclear localization. CRP and the control protein human serum albumin were FITC-conjugated and microinjected into living VERO cells. The cells were incubated at 37 degrees C for 15 min and then examined by fluorescence microscopy. Nuclear localization of CRP but not albumin was rapid and a high nuclear to cytoplasmic ratio was seen, consistent with active nuclear transport. Incubation at reduced temperature inhibited nuclear uptake by CRP. A synthetic peptide, RKSLKK, from the CRP sequence, when coupled to FITC-albumin, also mediated nuclear localization. Nuclear localization of the related protein, serum amyloid P component, was also seen and a homologous nuclear localization signal was identified. Because CRP was previously demonstrated to inhibit RNA transcription and enhance chromatin degradation it is proposed that CRP may play a unique role in injured cells to alter processing of damaged nuclei. Biochemical, structural and sequence comparisons between the CRP/serum amyloid P component family of proteins (pentraxins) and the nucleoplasmin/B23 family of proteins showed regions of sequence homology that may be related to their shared cyclic pentameric structure.
Du Clos
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VA Medical Center, Albuquerque, NM 87108.
Mold
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Stump
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D000595:Amino Acid Sequence; D001692:Biological Transport; D002097:C-Reactive Protein / Q000032:analysis*; D002467:Cell Nucleus / Q000737:chemistry*; D006801:Humans; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism; D056489:Nucleoplasmins; D010750:Phosphoproteins; D012709:Serum Albumin / Q000378:metabolism; D000683:Serum Amyloid P-Component / Q000378:metabolism
D009687:Nuclear Proteins; D056489:Nucleoplasmins; D010750:Phosphoproteins; D012709:Serum Albumin; D000683:Serum Amyloid P-Component; D002097:C-Reactive Protein