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Science 309 (5739): 1390-1394

Copyright © 2005 by the American Association for the Advancement of Science

Circadian Clock Control by SUMOylation of BMAL1

Luca Cardone,1 Jun Hirayama,1 Francesca Giordano,1 Teruya Tamaru,2 Jorma J. Palvimo,3* Paolo Sassone-Corsi1{dagger}

Abstract: The molecular machinery that governs circadian rhythmicity is based on clock proteins organized in regulatory feedback loops. Although posttranslational modification of clock proteins is likely to finely control their circadian functions, only limited information is available to date. Here, we show that BMAL1, an essential transcription factor component of the clock mechanism, is SUMOylated on a highly conserved lysine residue (Lys259) in vivo. BMAL1 shows a circadian pattern of SUMOylation that parallels its activation in the mouse liver. SUMOylation of BMAL1 requires and is induced by CLOCK, the heterodimerization partner of BMAL1. Ectopic expression of a SUMO-deficient BMAL1 demonstrates that SUMOylation plays an important role in BMAL1 circadian expression and clock rhythmicity. This reveals an additional level of regulation within the core mechanism of the circadian clock.

1 Institut de Génétique et de Biologie Moléculaire et Cellulaire, 1 rue Laurent Fries, 67404 Illkirch, Strasbourg, France.
2 Department of Physiology, Toho University School of Medicine, 5-21-16 Ohmori-nishi Ohta-ku, Tokyo 143-8540, Japan.
3 Biomedicum Helsinki, Institute of Biomedicine, Post Office Box 63, University of Helsinki, 00014 Helsinki, Finland.

* Present address: Department of Medical Biochemistry, University of Kuopio, 70211 Kuopio, Finland.

{dagger} To whom correspondence should be addressed. E-mail: paolosc{at}igbmc.u-strasbg.fr


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