Modification of nuclear lamin proteins by a mevalonic acid derivative occurs in reticulocyte lysates and requires the cysteine residue of the C-terminal CXXM motif.

Recent evidence suggests that the conserved COOH-terminal CaaX motif of nuclear lamins may play a role in targeting newly synthesized proteins to the nuclear envelope. We have shown previously that in rabbit reticulocyte lysates the cysteine residue of the CaaX motif of chicken lamin B2 is necessary for incorporation of a derivative of mevalonic acid, the precursor of isoprenoids. Here we have analyzed the properties of normal and mutated forms of chicken lamin B2 stably expressed in mouse L cells. Mutation of the cysteine residue of the CaaX motif to alanine or introduction of a stop codon immediately after the cysteine residue was found to abolish both isoprenylation and carboxyl methylation of transfected lamin B2. Concomitantly, although nuclear import of the mutant lamin B2 proteins was preserved, their association with the inner nuclear membrane was severely impaired. From these results we conclude that the COOH-terminal CaaX motif is required for isoprenylation and carboxyl methylation of lamins in vivo, and that these modifications are important for association of B-type lamins with the nucleoplasmic surface of the inner nuclear membrane.

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Synergism between a dietary flavonoid and butyric acid derivative in correcting chloride secretory defect in cystic fibrosis pancreatic duct cells

Gastroenterology ◽

10.1016/s0016-5085(01)81676-0 ◽

2001 ◽

Vol 120 (5) ◽

pp. A337-A337

Author(s):

T NGUYEN ◽

S PERRINE ◽

U KIM

Keyword(s):

Cystic Fibrosis ◽

Pancreatic Duct ◽

Acid Derivative ◽

Butyric Acid ◽

Duct Cells ◽

Pancreatic Duct Cells ◽

Dietary Flavonoid

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An usnic acid derivative as new tweezer for non-covalent aromatic interaction complex

Planta Medica ◽

10.1055/s-0028-1084759 ◽

2008 ◽

Vol 74 (09) ◽

Author(s):

B Legouin ◽

M Chollet-Krugler ◽

S Tomasi ◽

P Uriac ◽

P van de Weghe

Keyword(s):

Acid Derivative ◽

Usnic Acid ◽

Aromatic Interaction

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Mutations which Introduce Free Cysteine Residues in the Gla-Domain of Vitamin K Dependent Proteins Result in the Formation of Complexes with α1-Microglobulin

Thrombosis and Haemostasis ◽

10.1055/s-0038-1650223 ◽

1996 ◽

Vol 75 (01) ◽

pp. 070-075 ◽

Cited By ~ 20

Author(s):

E G C Wojcik ◽

P Simioni ◽

M v d Berg ◽

A Girolami ◽

R M Bertina

Keyword(s):

Vitamin K ◽

Protein C ◽

Cysteine Residue ◽

Factor Ix ◽

Disulphide Bond ◽

Clotting Factors ◽

High Molecular Weight Complex ◽

Low Concentrations ◽

Gla Domain ◽

Formation Of Complexes

SummaryWe have previously described a genetic factor IX variant (Cys18→Arg) for which we demonstrated that it had formed a heterodimer with armicroglobulin through formation of a disulphide bond with the remaining free cysteine residue of the disrupted disulphide bond in the Gla-domain of factor IX. Recently, we observed a similar high molecular weight complex for a genetic protein C variant (Arg-1→Cys). Both the factor IX and the protein C variants have a defect in the calcium induced conformation. In this study we show that the aminoterminus of this protein C variant is prolonged with one amino acid, cysteine. This protein C variant, as well as protein C variants with Arg9→Cys and Ser12→Cys mutations which also carry a free cysteine residue, are shown to be present in plasma as a complex with α1-microglobulin. A prothrombin variant with a Tyr44→Cys mutation, had not formed such a complex. Furthermore, complexes between normal vitamin K-dependent clotting factors and α1-microglobulin were shown to be present in plasma at low concentrations. The data suggest that the presence of an unpaired cysteine residue in the propeptide or the N-terminal half of the Gla-domain has strongly promoted the formation of a complex with α1-microglobulin in the variants.

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