Abstract
Post-translational modifications of one or more central "clock" proteins, most notably time-of-day-dependent changes in phosphorylation, are critical for setting the pace of circadian (y24 h) clocks. In animals, PERIOD (PER) proteins are the key state variable regulating circadian clock speed and undergo daily changes in abundance and cytoplasmic-nuclear distribution that are partly driven by a complex phosphorylation program. Here, we identify O-GlcNAcylation (O-GlcNAc) as a critical post-translational modification in circadian regulation that also contributes to setting clock speed. Knockdown or overexpression of Drosophila O-GlcNAc transferase (ogt) in clock cells either shortens or lengthens circadian behavioral rhythms, respectively. The Drosophila PERIOD protein (dPER) is a direct target of OGT and undergoes daily changes in O-GlcNAcylation, a modification that is mainly observed during the first half of the night, when dPER is predominantly located in the cytoplasm. Intriguingly, the timing of when dPER translocates from the cytoplasm to the nucleus is advanced or delayed in flies, wherein ogt expression is reduced or increased, respectively. Our results suggest that O-GlcNAcylation of dPER contributes to setting the correct pace of the clock by delaying the timing of dPER nuclear entry. In addition, OGT stabilizes dPER, suggesting that O-GlcNAcylation has multiple roles in circadian timing systems.
| Original language | English |
|---|---|
| Pages (from-to) | 490-502 |
| Number of pages | 13 |
| Journal | Genes and Development |
| Volume | 26 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - 2012 Mar 1 |
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All Science Journal Classification (ASJC) codes
- Genetics
- Developmental Biology
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A role for O-GlcNAcylation in setting circadian clock speed. / Kim, Eun Young; Jeong, Eun Hee; Park, Sujin; Jeong, Hyun Jeong; Edery, Isaac; Cho, Jin Won.
In: Genes and Development, Vol. 26, No. 5, 01.03.2012, p. 490-502.Research output: Contribution to journal › Article
TY - JOUR
T1 - A role for O-GlcNAcylation in setting circadian clock speed
AU - Kim, Eun Young
AU - Jeong, Eun Hee
AU - Park, Sujin
AU - Jeong, Hyun Jeong
AU - Edery, Isaac
AU - Cho, Jin Won
PY - 2012/3/1
Y1 - 2012/3/1
N2 - Post-translational modifications of one or more central "clock" proteins, most notably time-of-day-dependent changes in phosphorylation, are critical for setting the pace of circadian (y24 h) clocks. In animals, PERIOD (PER) proteins are the key state variable regulating circadian clock speed and undergo daily changes in abundance and cytoplasmic-nuclear distribution that are partly driven by a complex phosphorylation program. Here, we identify O-GlcNAcylation (O-GlcNAc) as a critical post-translational modification in circadian regulation that also contributes to setting clock speed. Knockdown or overexpression of Drosophila O-GlcNAc transferase (ogt) in clock cells either shortens or lengthens circadian behavioral rhythms, respectively. The Drosophila PERIOD protein (dPER) is a direct target of OGT and undergoes daily changes in O-GlcNAcylation, a modification that is mainly observed during the first half of the night, when dPER is predominantly located in the cytoplasm. Intriguingly, the timing of when dPER translocates from the cytoplasm to the nucleus is advanced or delayed in flies, wherein ogt expression is reduced or increased, respectively. Our results suggest that O-GlcNAcylation of dPER contributes to setting the correct pace of the clock by delaying the timing of dPER nuclear entry. In addition, OGT stabilizes dPER, suggesting that O-GlcNAcylation has multiple roles in circadian timing systems.
AB - Post-translational modifications of one or more central "clock" proteins, most notably time-of-day-dependent changes in phosphorylation, are critical for setting the pace of circadian (y24 h) clocks. In animals, PERIOD (PER) proteins are the key state variable regulating circadian clock speed and undergo daily changes in abundance and cytoplasmic-nuclear distribution that are partly driven by a complex phosphorylation program. Here, we identify O-GlcNAcylation (O-GlcNAc) as a critical post-translational modification in circadian regulation that also contributes to setting clock speed. Knockdown or overexpression of Drosophila O-GlcNAc transferase (ogt) in clock cells either shortens or lengthens circadian behavioral rhythms, respectively. The Drosophila PERIOD protein (dPER) is a direct target of OGT and undergoes daily changes in O-GlcNAcylation, a modification that is mainly observed during the first half of the night, when dPER is predominantly located in the cytoplasm. Intriguingly, the timing of when dPER translocates from the cytoplasm to the nucleus is advanced or delayed in flies, wherein ogt expression is reduced or increased, respectively. Our results suggest that O-GlcNAcylation of dPER contributes to setting the correct pace of the clock by delaying the timing of dPER nuclear entry. In addition, OGT stabilizes dPER, suggesting that O-GlcNAcylation has multiple roles in circadian timing systems.
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UR - http://www.scopus.com/inward/citedby.url?scp=84863230299&partnerID=8YFLogxK
U2 - 10.1101/gad.182378.111
DO - 10.1101/gad.182378.111
M3 - Article
C2 - 22327476
AN - SCOPUS:84863230299
VL - 26
SP - 490
EP - 502
JO - Genes and Development
JF - Genes and Development
SN - 0890-9369
IS - 5
ER -