A mutation which disrupts the hydrophobic core of the signal peptide of bilirubin UDP‐glucuronosyltransferase, an endoplasmic reticulum membrane protein, causes Crigler‐Najjar type IIs

FEBS Letters

Seppen, Jurgen¹  Bosma, Piter J.¹  Steenken, Edmee¹  Oude Elferink, Ronald P.J.¹  Lindhout, Dick² 

[1] Department of Gastrointestinal and Liver Diseases, FO-116, Academic Medical Centre, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands;Department of Clinical Genetics, Faculty of Medicine, Erasmus University, Rotterdam, The Netherlands

关键词: Bilirubin;    UDP-glucuronosyltransferase;    Signal peptide;    Endoplasmic reticulum;    Crigler-Najjar;    B-UGT;    bilirubin UDP-glucuronosyltransferase;    CN;    Crigler-Najjar disease;    ER;    endoplasmic reticulum;    HPLC;    high pressure liquid chromatography;    PCR;    polymerase chain reaction;    SDS PAGE;    sodium dodecyl sulfate polyacrylamide gel electrophoresis;    UGT;    UDP-glucuronosyltransferase;    SRP;    signal recognition particle;   

DOI  :  10.1016/0014-5793(96)00677-1

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Crigler-Najjar (CN) disease is caused by a deficiency of the hepatic enzyme, bilirubin UDP-glucuronosyltransferase (B-UGT). We have found two CN type II patients, who were homozygous for a leucine to arginine transition at position 15 of B-UGT1. This mutation is expected to disrupt the hydrophobic core of the signal peptide of B-UGT1. Wild type and mutant B-UGT cDNAs were transfected in COS cells. Mutant and wild type mRNA were formed in equal amounts. The mutant protein was expressed with 0.5% efficiency, as compared to wild type. Mutant and wild type mRNAs were translated in vitro. Wild type transferase is processed by microsomes, no processing of the mutant protein was observed.

【 授权许可】

Unknown