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.
Yamakuni
T
T
Mitsubishi Kasei Institute of Life Sciences, 11 Minamiooya, Machida, Tokyo 194-8511, Japan. yamakuni@libra.ls.m-kagaku.co.jp
Yamamoto
T
T
Hoshino
M
M
Song
S Y
SY
Yamamoto
H
H
Kunikata-Sumitomo
M
M
Minegishi
A
A
Kubota
M
M
Ito
M
M
Konishi
S
S
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