title: Beta1,4-galactosyltransferase and lactose biosynthesis: recruitment of a housekeeping gene from the nonmammalian vertebrate gene pool for a mammary gland specific function.
abstract: Beta1,4-galactosyltransferase (beta4GalT-I) is a constitutively expressed trans-Golgi enzyme, widely distributed in vertebrates, which synthesizes the beta4-N-acetyllactosamine structure commonly found in glycoconjugates. In mammals beta4GalT-I has been recruited for a second biosynthetic function, the production of lactose; this function takes place exclusively in the lactating mammary gland. In preparation for lactose biosynthesis, beta4GalT-I enzyme levels are increased significantly. We show that mammals have evolved a two-step mechanism to achieve this increase. In step one there is a switch to the use of a second transcriptional start site, regulated by a stronger, mammary gland-restricted promoter. The transcript produced is distinguished from its housekeeping counterpart by the absence of approximately 180 nt of 5'-untranslated sequence. In step two, this truncated transcript is translated more efficiently, relative to the major transcript expressed in all other somatic tissues.
authors.affiliation: Johns Hopkins University School of Medicine, The Cell Structure and Function Laboratory, Oncology Center, Baltimore, Maryland 21287-8937, USA. nshaper@welchlink.welch.jhu.edu
authors.forename: N L
authors.initials: NL
authors.lastname: Shaper
authors.forename: M
authors.initials: M
authors.lastname: Charron
authors.forename: N W
authors.initials: NW
authors.lastname: Lo
authors.forename: J H
authors.initials: JH
authors.lastname: Shaper
mesh_terms: D000818:Animals; D005260:Female; D005788:Gene Pool; D006801:Humans; D007785:Lactose / Q000096:biosynthesis*; D007788:Lactose Synthase / Q000235:genetics* / Q000378:metabolism*; D008322:Mammals; D008321:Mammary Glands, Animal / Q000201:enzymology*; D011401:Promoter Regions, Genetic; D014714:Vertebrates / Q000235:genetics*
chemical_list: D007788:Lactose Synthase; D007785:Lactose