A novel meprin beta' mRNA in mouse embryonal and human colon carcinoma cells.
Meprins, metalloendopeptidases of the astacin family, are composed of alpha and/or beta subunits and are expressed at high levels in mammalian renal and intestinal brushborder membranes. Only one mRNA has been identified previously for each of the subunits in adult human and rodent tissues; a 3.6-kilobase message for the alpha subunit and a 2.5-kilobase message for the beta subunit. The present study reports that a larger beta subunit message (2.7 kilobases, referred to as beta'), and no alpha subunit message, is expressed in embryonal carcinoma cell lines, F9 and Nulli-SSC1, and in human colon adenocarcinoma cells, HT-28-18-C1. Furthermore, in Nulli-SSC1 cells, the beta isoform is induced by the morphogen retinoic acid. The beta' isoform differs from beta only in a portion of the 5'-coding (corresponding to the signal and prosequence domains of the protein) and noncoding region. Only one gene was found for the beta subunit in the mouse and human genome. The deduced amino acid sequence of beta' has no homology with beta in the first 35 NH2-terminal residues, but the two sequences are identical after that. In vitro translation experiments indicated that the size of the protein product of beta' cDNA was similar to that of the beta cDNA protein product, and, in the presence of microsomal membranes, both were glycosylated. These studies indicate that the messages for the meprin beta and beta' subunit result from differential promoter usage and alternate splicing. Expression of the two isoforms may be regulated differentially depending on cell type and/or differentiation state of the cell.
Dietrich
J M
JM
Department of Biochemistry and Molecular Biology, Pennsylvania State University College of Medicine, Hershey 17033, USA.
Jiang
W
W
Bond
J S
JS
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D018236:Carcinoma, Embryonal / Q000201:enzymology; D003110:Colonic Neoplasms / Q000201:enzymology; D018507:Gene Expression Regulation, Developmental; D015972:Gene Expression Regulation, Neoplastic; D005796:Genes; D006801:Humans; D007527:Isoenzymes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D008666:Metalloendopeptidases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D012995:Solubility; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D007527:Isoenzymes; D008565:Membrane Proteins; D012333:RNA, Messenger; D014212:Tretinoin; D008666:Metalloendopeptidases; C095663:meprin B