[14-3-3 proteins--a role in the regulation of melatonin biosynthesis].
14-3-3 proteins compose a large family of proteins that exist primarily as homo- and heterodimers within all eukaryotic cells. They are engaged in the regulation of numerous cellular processes, including melatonin biosynthesis. Melatonin, the hormone of darkness, is synthesized in a diurnal or circadian rhythm, with high levels at night. It has been demonstrated that cAMP levels and PKA activity in melatonin-synthesizing cells (pinealocytes and retinal photoreceptors) increase at night. PKA phosphorylates serotonin N-acetyltransferase (AANAT; the penultimate and key regulatory enzyme in melatonin biosynthesis pathway) at its N- (Thr31) and C-(Ser205)terminal region. Phosphorylated of AANAT bind to 14-3-3 proteins. The formation of pAANAT/14-3-3 complex stabilizes the enzyme and protects it against proteolytic destruction. Furthermore, this complex induces allosteric changes of the AANAT molecule resulting in an increase of the enzyme activity; this in turn enhances melatonin production by several fold. Exposure to light at night decreases intracellular cAMP level with concomitant dephosphorylation of pAANAT, its dissociation from 14-3-3 dimers, proteosomal proteolysis of free AANAT molecules, and finally turning off the melatonin production.
Rosiak
Jolanta
J
Centrum Biologii Medycznej Polskiej Akademii Nauk w Lodzi, Lódź. jrosiak@cbm.pan.pl
Zawilska
Jolanta Barbara
JB
D048948:14-3-3 Proteins / Q000378:metabolism*; D000818:Animals; D047068:Arylalkylamine N-Acetyltransferase / Q000187:drug effects / Q000378:metabolism*; D002940:Circadian Rhythm / Q000502:physiology; D000242:Cyclic AMP / Q000378:metabolism*; D003624:Darkness; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D008027:Light; D008550:Melatonin / Q000096:biosynthesis*; D008954:Models, Biological; D017440:Photoperiod; D011487:Protein Conformation
D048948:14-3-3 Proteins; D004791:Enzyme Inhibitors; D000242:Cyclic AMP; D047068:Arylalkylamine N-Acetyltransferase; D008550:Melatonin