Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.1.3.16 (
calcineurin
)
17,112
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Circadian rhythms are generated by endogenous pacemakers that rely on transcriptional-translational feedback mechanisms conserved among species. In Drosophila, the stability of a key pacemaker protein PERIOD (PER) is tightly controlled by changes in phosphorylation status. A number of molecular players have been implicated in PER destabilization by promoting PER progressive phosphorylation. On the other hand, there have been few reports describing mechanisms that stabilize PER by delaying PER hyperphosphorylation. Here we report that the protein Suppressor of Ras (
SUR-8
) regulates circadian locomotor rhythms by stabilizing PER. Depletion of
SUR-8
from circadian neurons lengthened the circadian period by about 2 hours and decreased PER abundance, whereas its overexpression led to arrhythmia and an increase in PER. Specifically
SUR-8
promotes the stability of PER through phosphorylation regulation. Interestingly, downregulation of the
protein phosphatase
1 catalytic subunit PP1-87B recapitulated the phenotypes of
SUR-8
depletion. We found that
SUR-8
facilitates interactions between PP1-87B and PER. Depletion of
SUR-8
decreased the interaction of PER and PP1-87B, which supports the role of
SUR-8
as a scaffold protein. Interestingly, the interaction between
SUR-8
and PER is temporally regulated:
SUR-8
has more binding to PER at night than morning. Thus, our results indicate that
SUR-8
interacts with PP1-87B to control PER stability to regulate circadian rhythms.
...
PMID:SUR-8 interacts with PP1-87B to stabilize PERIOD and regulate circadian rhythms in Drosophila. 3171 Jun 5
