title: Drosophila peptidyl-prolyl isomerase Pin1 modulates circadian rhythms via regulating levels of PERIOD.
abstract: In animal circadian clock machinery, the phosphorylation program of PERIOD (PER) leads to the spatio-temporal regulation of diverse PER functions, which are crucial for the maintenance of ~24-hr circadian rhythmicity. The peptidyl-prolyl isomerase PIN1 modulates the diverse functions of its substrates by inducing conformational changes upon recognizing specific phosphorylated residues. Here, we show that overexpression of Drosophila pin1, dodo (dod), lengthens the locomotor behavioral period. Using Drosophila S2 cells, we demonstrate that Dod associates preferentially with phosphorylated species of PER, which delays the phosphorylation-dependent degradation of PER. Consistent with this, PER protein levels are higher in flies overexpressing dod. Taken together, we suggest that Dod plays a role in the maintenance of circadian period by regulating PER metabolism.
authors.affiliation: Neuroscience Graduate Program, Department of Biomedical Sciences, Ajou University School of Medicine, 164 Worldcup-ro, Yeongtong-gu, Suwon, Kyunggi-do, 443-380, Republic of Korea; Department of Brain Science, Ajou University School of Medicine, 164 Worldcup-ro, Yeongtong-gu, Suwon, Kyunggi-do, 443-380, Republic of Korea.
authors.forename: So Who
authors.initials: SW
authors.lastname: Kang
authors.affiliation: Neuroscience Graduate Program, Department of Biomedical Sciences, Ajou University School of Medicine, 164 Worldcup-ro, Yeongtong-gu, Suwon, Kyunggi-do, 443-380, Republic of Korea; Department of Brain Science, Ajou University School of Medicine, 164 Worldcup-ro, Yeongtong-gu, Suwon, Kyunggi-do, 443-380, Republic of Korea.
authors.forename: Euna
authors.initials: E
authors.lastname: Lee
authors.affiliation: Department of Brain Science, Ajou University School of Medicine, 164 Worldcup-ro, Yeongtong-gu, Suwon, Kyunggi-do, 443-380, Republic of Korea; Chronic Inflammatory Disease Research Center, Ajou University School of Medicine, 164 Worldcup-ro, Yeongtong-gu, Suwon, Kyunggi-do, 443-380, Republic of Korea.
authors.forename: Eunjoo
authors.initials: E
authors.lastname: Cho
authors.affiliation: Department of Brain Science, Ajou University School of Medicine, 164 Worldcup-ro, Yeongtong-gu, Suwon, Kyunggi-do, 443-380, Republic of Korea.
authors.forename: Ji Hye
authors.initials: JH
authors.lastname: Seo
authors.affiliation: College of Pharmacy, Dongguk University, 32 Donggukro, Ilsandonggu, Goyangsi, Gyeonggido, 410-820, Republic of Korea.
authors.forename: Hyuk Wan
authors.initials: HW
authors.lastname: Ko
authors.affiliation: Neuroscience Graduate Program, Department of Biomedical Sciences, Ajou University School of Medicine, 164 Worldcup-ro, Yeongtong-gu, Suwon, Kyunggi-do, 443-380, Republic of Korea; Department of Brain Science, Ajou University School of Medicine, 164 Worldcup-ro, Yeongtong-gu, Suwon, Kyunggi-do, 443-380, Republic of Korea; Chronic Inflammatory Disease Research Center, Ajou University School of Medicine, 164 Worldcup-ro, Yeongtong-gu, Suwon, Kyunggi-do, 443-380, Republic of Korea. Electronic address: ekim@ajou.ac.kr.
authors.forename: Eun Young
authors.initials: EY
authors.lastname: Kim
mesh_terms: D000818:Animals; D002460:Cell Line; D002940:Circadian Rhythm; D004330:Drosophila / Q000235:genetics / Q000502:physiology*; D029721:Drosophila Proteins / Q000378:metabolism*; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D019696:Peptidylprolyl Isomerase / Q000235:genetics / Q000378:metabolism*; D056950:Period Circadian Proteins / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D060066:Protein Interaction Maps; D059748:Proteolysis; D015854:Up-Regulation
chemical_list: D029721:Drosophila Proteins; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; C539040:PER protein, Drosophila; D056950:Period Circadian Proteins; D019696:Peptidylprolyl Isomerase; C000606849:dod protein, Drosophila
keywords: Circadian rhythms; Dodo; Drosophila; PERIOD; Peptidyl-prolyl isomerase; Pin1