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Molecular and Cellular Biology, November 2001, p. 7287-7294, Vol. 21, No. 21
Department of Neuroscience, Howard Hughes
Medical Institute, University of Pennsylvania Medical School,
Philadelphia, Pennsylvania 19104
Received 25 January 2001/Returned for modification 5 March
2001/Accepted 7 August 2001
Oscillations of the period (per) and
timeless (tim) gene products are an integral
part of the feedback loop that underlies circadian behavioral rhythms
in Drosophila melanogaster. Resetting this loop in
response to light requires the putative circadian photoreceptor
cryptochrome (CRY). We dissected the early events in photic resetting
by determining the mechanisms underlying the CRY response to light and
by investigating the relationship between CRY and the
light-induced ubiquitination of the TIM protein. In response to light,
CRY is degraded by the proteasome through a mechanism that requires
electron transport. Various CRY mutant proteins are not degraded,
and this suggests that an intramolecular conversion is required for
this light response. Light-induced TIM ubiquitination precedes CRY
degradation and is increased when electron transport is blocked. Thus,
inhibition of electron transport may "lock" CRY in an active state
by preventing signaling required either to degrade CRY or to convert it
to an inactive form. High levels of CRY block TIM ubiquitination,
suggesting a mechanism by which light-driven changes in CRY could
control TIM ubiquitination.
0270-7306/01/$04.00+0 DOI: 10.1128/MCB.21.21.7287-7294.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Photic Signaling by Cryptochrome in the Drosophila
Circadian System
*
Corresponding author. Mailing address: Howard Hughes
Medical Institute, Department of Neuroscience, University of
Pennsylvania Medical School, Philadelphia, PA 19104. Phone: (215)
573-2985. Fax: (215) 573-2015. E-mail:
amita{at}mail.med.upenn.edu.
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