Sialomucin complex (rat Muc4) is regulated by transforming growth factor beta in mammary gland by a novel post-translational mechanism.
Sialomucin complex (SMC, rat Muc4) is a heterodimeric glycoprotein complex consisting of a mucin subunit ASGP-1 (for ascites sialoglycoprotein-1) and a transmembrane subunit ASGP-2, produced from a single gene and precursor. SMC expression is tightly regulated in mammary gland; the level in lactating mammary gland is about 100-fold that in virgin gland. In rat mammary epithelial cells, SMC is post-transcriptionally regulated by Matrigel by inhibition of SMC precursor synthesis. SMC is also post-transcriptionally regulated by transforming growth factor-beta (TGFbeta). The repression of SMC expression by TGFbeta is rapid, is independent of TGFbeta-induced cell cycle arrest, and does not require new protein synthesis. Unlike Matrigel, TGFbeta does not reduce SMC protein synthesis, as SMC precursor accumulation is equivalent in TGFbeta-treated and untreated cells. Instead, SMC precursor in TGFbeta-treated cells is more persistent and does not become processed as rapidly into mature ASGP-1 and ASGP-2, indicating that TGFbeta disrupts processing of SMC precursor. These results indicate that SMC, a product of normal mammary gland and milk, is regulated by TGFbeta by a novel post-translational mechanism. Thus, SMC is regulated by multiple post-transcriptional mechanisms, which serve to repress potential deleterious effects of overexpression.
Price-Schiavi
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SA
Department of Cell Biology and Anatomy and Sylvester Comprehensive Cancer Center, University of Miami School of Medicine, Miami, Florida 33101, USA.
Zhu
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Aquinin
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Carraway
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KL
D000818:Animals; D002478:Cells, Cultured; D016384:Consensus Sequence; D003513:Cycloheximide / Q000494:pharmacology; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D007774:Lactation; D008321:Mammary Glands, Animal / Q000166:cytology / Q000378:metabolism*; D008325:Mammary Neoplasms, Experimental; D055264:Mucin-4; D009077:Mucins / Q000235:genetics* / Q000378:metabolism*; D011247:Pregnancy; D011499:Protein Processing, Post-Translational / Q000187:drug effects*; D011691:Puromycin / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D012795:Sialoglycoproteins / Q000096:biosynthesis / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014415:Tunicamycin / Q000494:pharmacology
C524658:MUC4 protein, human; C524660:Muc4 protein, rat; D055264:Mucin-4; D009077:Mucins; D012795:Sialoglycoproteins; D016212:Transforming Growth Factor beta; D014415:Tunicamycin; D011691:Puromycin; D003513:Cycloheximide