A novel protein containing Cdc10/SWI6 motifs regulates expression of mRNA encoding catecholamine biosynthesizing enzymes.
Catecholaminergic (dopaminergic, noradrenergic, and adrenergic) transmitter phenotypes require the cooperative actions of four biosynthetic enzymes: tyrosine hydroxylase, aromatic L-amino acid decarboxylase, dopamine beta-hydroxylase, and phenylethanolamine N-methyltransferase. Mechanisms that control expression of these enzymes in a transmitter phenotype-specific manner, however, are poorly understood. Here, we provide evidence that overexpression of a novel cdc10/SWI6 motif-containing protein, V-1, elicits the coordinate up-regulation of tyrosine hydroxylase, aromatic L-amino acid decarboxylase, and dopamine beta-hydroxylase mRNAs in the neuronal cell line PC12D, and as a result, catecholamine levels are increased. Furthermore, V-1 is strongly expressed in the cytoplasm of rat chromaffin cells of adrenal medulla. Thus, V-1 may act as a cytoplasmic protein/protein adapter and be involved in control of the catecholaminergic phenotype expression via an intracellular pathway signaling to the nucleus.
Mitsubishi Kasei Institute of Life Sciences, 11 Minamiooya, Machida, Tokyo 194-8511, Japan. yamakuni@libra.ls.m-kagaku.co.jp
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Yamakuni
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Yamamoto
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Hoshino
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Yamamoto
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Kunikata-Sumitomo
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Minegishi
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Kubota
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Ito
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Konishi
D000313:Adrenal Medulla / Q000166:cytology / Q000378:metabolism; D000818:Animals; D017089:Ankyrin Repeat; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000096:biosynthesis; D002395:Catecholamines / Q000096:biosynthesis*; D018797:Cell Cycle Proteins; D019439:Chromaffin Cells / Q000166:cytology / Q000378:metabolism; D003598:Cytoskeletal Proteins; D004299:Dopamine beta-Hydroxylase / Q000096:biosynthesis; D020558:GTP Phosphohydrolases; D015971:Gene Expression Regulation, Enzymologic; D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D016716:PC12 Cells; D051381:Rats; D020449:Repetitive Sequences, Amino Acid; D029702:Schizosaccharomyces pombe Proteins; D058112:Septins; D014157:Transcription Factors; D014446:Tyrosine 3-Monooxygenase / Q000096:biosynthesis; D015854:Up-Regulation
D002395:Catecholamines; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D029702:Schizosaccharomyces pombe Proteins; D014157:Transcription Factors; C061178:cdc10 protein, S pombe; C065700:myotrophin; D014446:Tyrosine 3-Monooxygenase; D004299:Dopamine beta-Hydroxylase; D020558:GTP Phosphohydrolases; C512894:Septin7 protein, rat; D058112:Septins; D001142:Aromatic-L-Amino-Acid Decarboxylases