The COP9 Signalosome is Required for Light-dependent TIM Degradation and Drosophila Clock Resetting

The COP9 Signalosome is Required for Light-dependent TIM Degradation and Drosophila Clock Resetting

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The circadian clock regulates aˆ¼24hr oscillations of biological processes and behavior in organisms ranging from bacteria to humans. These rhythms are driven by an internal molecular clock of cycling gene products, in which protein turnover via the ubiquitin-proteasome system is essential to generate aˆ¼24hr oscillations. In Drosophila, behavioral and molecular rhythms are entrained to external light cues via the ubiquitin-proteasome system, which mediates light-induced degradation of the essential clock protein TIMELESS (TIM). This study addresses the role of the COP9 Signalosome (CSN), a general regulator of protein degradation, in Drosophila circadian rhythms. The CSN is a protein complex initially found to be involved in light-mediated protein degradation during development of Arabidopsis seedlings. The light pathways that reset the Drosophila clock have intriguing parallels with light-mediated development in Arabidopsis, suggesting that the CSN could also be involved in regulating Drosophila light-dependent TIM degradation. My experiments show that TIM light-induced degradation is impaired in the pacemaker lateral neurons (LNs) of CSN4null and CSN5null mutant larvae, and with dominant-negative CSN5 transgenes. This decrease in TIM degradation contributes to reductions in behavioral phase shifts of flies with abolished/reduced CSN5 activity in LNs. The reductions in TIM degradation and behavioral phase shifts can be rescued by overexpression of JETLAG, the F-box protein required for light-mediated TIM degradation. Therefore, CSN and JET reside in a common pathway to control TIM degradation by light.Flies heterozygous for two copies of the Pdf0.5-Gal4 driver were used as controls (Pdf agt; +). Flies analyzed had either a wild type CSN5 transgene (UAS-CSNS^) or one of two UAS-CSN5 dominant negative transgenes (UASCSN5?


Title:The COP9 Signalosome is Required for Light-dependent TIM Degradation and Drosophila Clock Resetting
Author: Alyson Knowles
Publisher:ProQuest - 2008
ISBN-13:

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