A mutation in the 5′ untranslated region of the human α‐galactosidase A gene in high‐activity variants inhibits specific protein binding

FEBS Letters

Desnick, Robert J.²  Ehrlich, Melanie¹  Saifudeen, Zubaida¹ 

[1] Molecular and Cellular Biology Program, Mount Sinai School of Medicine, New York, NY 10029, USA;Department of Medical and Molecular Genetics, Mount Sinai School of Medicine, New York, NY 10029, USA

关键词: Transcription factor;    α-Galactosidase A;    Promoter sequence;    NF-κB;    DNA methylation;    α-Gal A;    α-galactosidase A;    WT;    wild-type;    EMSA;    electrophoretic mobility shift assay;    kb;    kilobase-pair;    bp;    base-pair;    5′ UT;    5′ untranslated;    Lwt;    specific protein binding site in the 5′ UT region of the WT α-GAL A gene;    Lmu;    mutant form of the Lwt site;   

DOI  :  10.1016/0014-5793(95)00891-C

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Recently, normal individuals were identified who had high levels of plasma α-galactosidase A activity and a G to A transition in the 5′ untranslated (5′ UT) region of the α-galactosidase A gene. Electrophoretic mobility shift assays revealed that the wild-type sequence at the site of this mutation complexed with specific nuclear proteins. A standard NF-κB site competed with the 5′ UT site for formation of these DNA-protein complexes. Complex formation was inhibited by the transition mutation. Therefore, the wild-type site might down-modulate expression of the α-galactosidase A gene from this 5′ untranslated region, which includes a previously described protein-binding site for another family of sequence-specific DNA-binding proteins, methylated DNA-binding protein.

【 授权许可】

Unknown