Tumor necrosis factor-α converting enzyme/ADAM 17 mediates MUC1 shedding Journal Article


Authors: Thathiah, A.; Blobel, C. P.; Carson, D. D.
Article Title: Tumor necrosis factor-α converting enzyme/ADAM 17 mediates MUC1 shedding
Abstract: MUC1 clearance from the uterine epithelial cell surface is a prerequisite for the creation of an environment conducive to embryo implantation. In some species, reduced mRNA levels along with metabolic turnover account for loss of MUC1 during the receptive phase throughout the uterine epithelium. In other species, MUC1 is rapidly lost solely at the site of blastocyst attachment, suggesting the action of a protease. Correlative studies also indicate the presence of soluble forms of MUC1 in cell culture supernatants in vitro and in bodily fluids in vivo. To characterize the proteolytic activity mediating MUC1 release, shedding of MUC1 was analyzed in a human uterine epithelial cell line (HES) that abundantly expresses and readily sheds MUC1. MUC1 release was stimulated by phorbol 12-myristate 13-acetate and was markedly inhibited by the synthetic peptide hydroxamate metalloprotease inhibitor, tumor necrosis factor-α protease inhibitor (TAPI), as well as by an endogenous inhibitor of matrix metalloproteases, tissue inhibitor of metalloproteases (TIMP)-3. These characteristics along with studies conducted with cell lines genetically deficient in various ADAMs (for a disintegrin and metalloprotease) identified tumor necrosis factor-α converting enzyme (TACE)/ADAM 17 as a MUC1 sheddase. Furthermore, both TACE and MUC1 were expressed in human uterine epithelia during the receptive phase, and co-immunoprecipitation experiments revealed a physical interaction between TACE and MUC1 in HES cells. These studies establish a proteolytic mechanism for MUC1 clearance from a human uterine epithelial cell line and identify TACE as a MUC1 sheddase.
Keywords: immunohistochemistry; unclassified drug; human cell; genetics; mouse; animal; cytology; metabolism; animals; mice; reverse transcription polymerase chain reaction; protein degradation; protein metabolism; protein protein interaction; cell line; drug effect; physiology; rna; drug antagonism; messenger rna; reverse transcriptase polymerase chain reaction; tumors; rna, messenger; nucleotide sequence; immunoprecipitation; hydroxamic acids; protein secretion; epithelium cell; epithelial cells; base sequence; mucin 1; dna primers; primer dna; biochemistry; proteinase inhibitor; uterus; enzymes; hydroxamic acid; endometrium; metalloproteinase; adam protein; adam proteins; tissue inhibitor of metalloproteinase 3; blastocyst; embryo implantation; phorbol 13 acetate 12 myristate; tetradecanoylphorbol acetate; dipeptides; cells; nidation; ca-15-3 antigen; ca 15-3 antigen; tumor necrosis factor alpha converting enzyme; dipeptide; metalloendopeptidases; humans; human; female; priority journal; article; tumor necrosis factor alpha protease inhibitor; n ((2 (hydroxyaminocarbonyl)methyl) 4 methylpentanoyl) 3 (2' naphthyl)alanylalanine, 2 aminoethylamide; n-((2-(hydroxyaminocarbonyl)methyl)-4-methylpentanoyl)-3-(2'-naphthyl)alanylalanine, 2-aminoethylamide; tumor necrosis factor-alpha convertase; tissue inhibitor of metalloproteinase-3
Journal Title: Journal of Biological Chemistry
Volume: 278
Issue: 5
ISSN: 0021-9258
Publisher: American Society for Biochemistry and Molecular Biology  
Date Published: 2003-01-31
Start Page: 3386
End Page: 3394
Language: English
DOI: 10.1074/jbc.M208326200
PUBMED: 12441351
PROVIDER: scopus
DOI/URL:
Notes: Export Date: 12 September 2014 -- Source: Scopus
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MSK Authors
  1. Carl Blobel
    52 Blobel