{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T19:17:47Z","timestamp":1772997467462,"version":"3.50.1"},"reference-count":39,"publisher":"The Endocrine Society","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2005,11,1]]},"abstract":"<jats:p>In this study, we investigated the effect of proteasomal inhibition on the induction of arylalkylamine-N-acetyltransferase (AA-NAT) enzyme in cultured rat pinealocytes, using two proteasome inhibitors, MG132 and clastolactacystin \u03b2-lactone (c-lact). Addition of c-lact or MG132 3 h after norepinephrine (NE) stimulation produced a significant increase in AA-NAT protein level and enzyme activity. However, when the proteasome inhibitors were added before or together with NE, significant reductions of the NE-induced aa-nat mRNA, protein, and enzyme activity were observed. A similar inhibitory effect of MG132 on aa-nat transcription was observed when cells were stimulated by dibutyryl cAMP, indicating an effect distal to a post-cAMP step. The inhibitory effect of MG132 on adrenergic-induced aa-nat transcription was long lasting because it remained effective after 14 h of washout and appeared specific for aa-nat because the induction of another adrenergic-regulated gene, MAPK phosphatase-1, by NE was not affected. Time-profile studies revealed that the inhibitory effect of MG132 on NE-stimulated aa-nat induction was detected after 1 h, suggesting accumulation of a protein repressor as a possible mechanism of action. This possibility was also supported by the finding that the inhibitory effect of c-lact on NE-induced aa-nat induction was markedly reduced by cycloheximide, a protein synthesis inhibitor. Together, these results support an important role of proteasomal proteolysis in the adrenergic-mediated induction of aa-nat transcription through its effect on a protein repressor.<\/jats:p>","DOI":"10.1210\/en.2005-0642","type":"journal-article","created":{"date-parts":[[2005,8,12]],"date-time":"2005-08-12T01:48:28Z","timestamp":1123811308000},"page":"4795-4803","source":"Crossref","is-referenced-by-count":8,"title":["Proteasomal Proteolysis in the Adrenergic Induction of Arylalkylamine-N-Acetyltransferase in Rat Pinealocytes"],"prefix":"10.1210","volume":"146","author":[{"given":"David L.","family":"Terriff","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Constance L.","family":"Chik","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donald M.","family":"Price","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anthony K.","family":"Ho","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","reference":[{"key":"2020071612370935000_R1","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1073\/pnas.80.2.599","article-title":"Postsynaptic \u03b1-adrenergic receptors potentiate the \u03b2-adrenergic stimulation of pineal serotonin N-acetyltransferase.","volume":"80","author":"Klein","year":"1983","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020071612370935000_R2","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1126\/science.168.3934.979","article-title":"Melatonin synthesis: adenosine 3\u2032,5\u2032-monophosphate and norepinephrine stimulate N-acetyltransferase.","volume":"168","author":"Klein","year":"1970","journal-title":"Science"},{"key":"2020071612370935000_R3","first-page":"241","article-title":"Pineal gland: stimulation of melatonin production by norepinephrine involves cyclic AMP-mediated stimulation of N-acetyltransferase.","volume":"3","author":"Klein","year":"1970","journal-title":"Adv Biochem Psychopharmacol"},{"key":"2020071612370935000_R4","first-page":"439","article-title":"Norepinephrine stimulation of pineal cyclic AMP response element-binding protein phosphorylation: primary role of a \u03b2-adrenergic receptor\/cyclic AMP mechanism.","volume":"47","author":"Roseboom","year":"1995","journal-title":"Mol Pharmacol"},{"key":"2020071612370935000_R5","doi-asserted-by":"crossref","first-page":"6979","DOI":"10.1074\/jbc.272.11.6979","article-title":"The rat arylalkylamine N-acetyltransferase gene promoter. cAMP activation via a cAMP-responsive element-CCAAT complex.","volume":"272","author":"Baler","year":"1997","journal-title":"J Biol Chem"},{"key":"2020071612370935000_R6","doi-asserted-by":"crossref","first-page":"6682","DOI":"10.1073\/pnas.83.18.6682","article-title":"Identification of a cyclic-AMP-responsive element within the rat somatostatin gene.","volume":"83","author":"Montminy","year":"1986","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020071612370935000_R7","doi-asserted-by":"crossref","first-page":"17746","DOI":"10.1074\/jbc.271.30.17746","article-title":"Identification and characterization of a novel transcriptional activation domain in the CREB-binding protein.","volume":"271","author":"Bisotto","year":"1996","journal-title":"J Biol Chem"},{"key":"2020071612370935000_R8","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1038\/378783a0","article-title":"Diurnal variation in mRNA encoding serotonin N-acetyltransferase in pineal gland.","volume":"378","author":"Borjigin","year":"1995","journal-title":"Nature"},{"key":"2020071612370935000_R9","doi-asserted-by":"crossref","first-page":"3033","DOI":"10.1210\/endo.137.7.8770929","article-title":"Melatonin synthesis: analysis of the more than 150-fold nocturnal increase in serotonin N-acetyltransferase messenger ribonucleic acid in the rat pineal gland.","volume":"137","author":"Roseboom","year":"1996","journal-title":"Endocrinology"},{"key":"2020071612370935000_R10","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1002\/(SICI)1521-1878(200005)22:5<442::AID-BIES6>3.0.CO;2-Q","article-title":"Ubiquitin-mediated proteolysis: biological regulation via destruction.","volume":"22","author":"Ciechanover","year":"2000","journal-title":"Bioessays"},{"key":"2020071612370935000_R11","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1146\/annurev.biochem.68.1.1015","article-title":"The 26S proteasome: a molecular machine designed for controlled proteolysis.","volume":"68","author":"Voges","year":"1999","journal-title":"Annu Rev Biochem"},{"key":"2020071612370935000_R12","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1038\/80992","article-title":"A gated channel into the proteasome core particle.","volume":"7","author":"Groll","year":"2000","journal-title":"Nat Struct Biol"},{"key":"2020071612370935000_R13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0003-9861(03)00197-8","article-title":"Ubiquitin-independent proteolytic functions of the proteasome.","volume":"415","author":"Orlowski","year":"2003","journal-title":"Arch Biochem Biophys"},{"key":"2020071612370935000_R14","doi-asserted-by":"crossref","first-page":"15727","DOI":"10.1074\/jbc.M410876200","article-title":"Proteasome inhibition alters glucose-stimulated (pro)insulin secretion and turnover in pancreatic \u03b2-cells.","volume":"280","author":"Kitiphongspattana","year":"2005","journal-title":"J Biol Chem"},{"key":"2020071612370935000_R15","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1096\/fj.04-2726fje","article-title":"Characterization of signaling pathways leading to Fas expression induced by TNF-\u03b1: pivotal role of NF-\u03baB.","volume":"19","author":"Starace","year":"2005","journal-title":"FASEB J"},{"key":"2020071612370935000_R16","doi-asserted-by":"crossref","first-page":"25267","DOI":"10.1074\/jbc.M501014200","article-title":"Selective induction of a tumor marker glutathione S-transferase P1 by proteasome inhibitors.","volume":"280","author":"Usami","year":"2005","journal-title":"J Biol Chem"},{"key":"2020071612370935000_R17","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1038\/nsb1005","article-title":"Cellular stabilization of the melatonin rhythm enzyme induced by nonhydrolyzable phosphonate incorporation.","volume":"10","author":"Zheng","year":"2003","journal-title":"Nat Struct Biol"},{"key":"2020071612370935000_R18","doi-asserted-by":"crossref","first-page":"1222","DOI":"10.1073\/pnas.0406871102","article-title":"Melatonin synthesis: 14-3-3-dependent activation and inhibition of arylalkylamine N-acetyltransferase mediated by phosphoserine-205.","volume":"102","author":"Ganguly","year":"2005","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020071612370935000_R19","doi-asserted-by":"crossref","first-page":"1358","DOI":"10.1126\/science.279.5355.1358","article-title":"Melatonin production: proteasomal proteolysis in serotonin N-acetyltransferase regulation.","volume":"279","author":"Gastel","year":"1998","journal-title":"Science"},{"key":"2020071612370935000_R20","doi-asserted-by":"crossref","first-page":"1483","DOI":"10.1210\/endo-103-4-1483","article-title":"A suspension culture of pinealocytes: regulation of N-acetyltransferase activity.","volume":"103","author":"Buda","year":"1978","journal-title":"Endocrinology"},{"key":"2020071612370935000_R21","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1038\/227680a0","article-title":"Cleavage of structural proteins during the assembly of the head of bacteriophage T4.","volume":"227","author":"Laemmli","year":"1970","journal-title":"Nature"},{"key":"2020071612370935000_R22","doi-asserted-by":"crossref","first-page":"5723","DOI":"10.1210\/en.2004-0880","article-title":"Norepinephrine induction of mitogen-activated protein kinase phosphatase-1 expression in rat pinealocytes: distinct roles of \u03b1- and \u03b2-adrenergic receptors.","volume":"145","author":"Price","year":"2004","journal-title":"Endocrinology"},{"key":"2020071612370935000_R23","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/j.febslet.2004.09.083","article-title":"Mitogen-activated protein kinase phosphatase-1 (MKP-1): &gt;100-fold nocturnal and norepinephrine-induced changes in the rat pineal gland.","volume":"577","author":"Price","year":"2004","journal-title":"FEBS Lett"},{"key":"2020071612370935000_R24","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1006\/abbi.1995.1381","article-title":"Sodium dodecyl sulfate (SDS) activation of the 20S proteasome in rat liver.","volume":"321","author":"Shibatani","year":"1995","journal-title":"Arch Biochem Biophys"},{"key":"2020071612370935000_R25","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1016\/S0006-2952(01)00839-5","article-title":"Potentiation of cyclic AMP and cyclic GMP accumulation by p38 mitogen-activated protein kinase (p38MAPK) inhibitors in rat pinealocytes.","volume":"62","author":"Ho","year":"2001","journal-title":"Biochem Pharmacol"},{"key":"2020071612370935000_R26","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1210\/en.2003-1170","article-title":"Inhibition of p38 mitogen-activated protein kinase enhances adrenergic-stimulated arylalkylamine N-acetyltransferase activity in rat pinealocytes.","volume":"145","author":"Man","year":"2004","journal-title":"Endocrinology"},{"key":"2020071612370935000_R27","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1126\/science.202027","article-title":"Pineal serotonin N-acetyltransferase activity: abrupt decrease in adenosine 3\u2032,5\u2032-monophosphate may be signal for \u201cturnoff.\u201d","volume":"199","author":"Klein","year":"1978","journal-title":"Science"},{"key":"2020071612370935000_R28","doi-asserted-by":"crossref","first-page":"8083","DOI":"10.1073\/pnas.141118798","article-title":"Role of a pineal cAMP-operated arylalkylamine N-acetyltransferase\/14-3-3-binding switch in melatonin synthesis.","volume":"98","author":"Ganguly","year":"2001","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020071612370935000_R29","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1016\/S1074-5521(01)00056-4","article-title":"Proteasome inhibitors: from research tools to drug candidates.","volume":"8","author":"Kisselev","year":"2001","journal-title":"Chem Biol"},{"key":"2020071612370935000_R30","doi-asserted-by":"crossref","first-page":"21517","DOI":"10.1074\/jbc.M301032200","article-title":"Inhibition of proteasome activity induces concerted expression of proteasome genes and de novo formation of mammalian proteasomes.","volume":"278","author":"Meiners","year":"2003","journal-title":"J Biol Chem"},{"key":"2020071612370935000_R31","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1038\/365314a0","article-title":"Adrenergic signals direct rhythmic expression of transcriptional repressor CREM in the pineal gland.","volume":"365","author":"Stehle","year":"1993","journal-title":"Nature"},{"key":"2020071612370935000_R32","doi-asserted-by":"crossref","first-page":"3326","DOI":"10.1523\/JNEUROSCI.19-09-03326.1999","article-title":"Transcription factors in neuroendocrine regulation: rhythmic changes in pCREB and ICER levels frame melatonin synthesis.","volume":"19","author":"Maronde","year":"1999","journal-title":"J Neurosci"},{"key":"2020071612370935000_R33","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1038\/380162a0","article-title":"Severe impairment of spermatogenesis in mice lacking the CREM gene.","volume":"380","author":"Blendy","year":"1996","journal-title":"Nature"},{"key":"2020071612370935000_R34","doi-asserted-by":"crossref","first-page":"14140","DOI":"10.1073\/pnas.93.24.14140","article-title":"Transcriptional control of circadian hormone synthesis via the CREM feedback loop.","volume":"93","author":"Foulkes","year":"1996","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020071612370935000_R35","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1002\/cne.20290","article-title":"Distribution of transcription factor inducible cyclic AMP early repressor (ICER) in rodent brain and pituitary.","volume":"478","author":"Kell","year":"2004","journal-title":"J Comp Neurol"},{"key":"2020071612370935000_R36","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1042\/bj3280037","article-title":"Degradation of the inducible cAMP early repressor (ICER) by the ubiquitin-proteasome pathway.","volume":"328","author":"Folco","year":"1997","journal-title":"Biochem J"},{"key":"2020071612370935000_R37","doi-asserted-by":"crossref","first-page":"5346","DOI":"10.1523\/JNEUROSCI.1460-04.2004","article-title":"Day-night changes in downstream regulatory antagonist modulator\/potassium channel interacting protein activity contribute to circadian gene expression in pineal gland.","volume":"24","author":"Link","year":"2004","journal-title":"J Neurosci"},{"key":"2020071612370935000_R38","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/S0248-4900(98)80004-X","article-title":"Rhythmic transcription: the molecular basis of circadian melatonin synthesis.","volume":"89","author":"Foulkes","year":"1997","journal-title":"Biol Cell"},{"key":"2020071612370935000_R39","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1016\/0092-8674(93)90532-U","article-title":"Inducibility and negative autoregulation of CREM: an alternative promoter directs the expression of ICER, an early response repressor.","volume":"75","author":"Molina","year":"1993","journal-title":"Cell"}],"container-title":["Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/endo\/article-pdf\/146\/11\/4795\/9023061\/endo4795.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/endo\/article-pdf\/146\/11\/4795\/9023061\/endo4795.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,7,16]],"date-time":"2020-07-16T20:56:34Z","timestamp":1594932994000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/endo\/article\/146\/11\/4795\/2499927"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,11,1]]},"references-count":39,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2005,11,1]]}},"URL":"https:\/\/doi.org\/10.1210\/en.2005-0642","relation":{},"ISSN":["0013-7227","1945-7170"],"issn-type":[{"value":"0013-7227","type":"print"},{"value":"1945-7170","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,11,1]]}}}