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Luca Cardone,1Jun Hirayama,1Francesca Giordano,1Teruya Tamaru,2Jorma J. Palvimo,3*Paolo Sassone-Corsi1
The molecular machinery that governs circadian rhythmicity isbased on clock proteins organized in regulatory feedback loops.Although posttranslational modification of clock proteins islikely to finely control their circadian functions, only limitedinformation 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 thatparallels its activation in the mouse liver. SUMOylation ofBMAL1 requires and is induced by CLOCK, the heterodimerizationpartner of BMAL1. Ectopic expression of a SUMO-deficient BMAL1demonstrates that SUMOylation plays an important role in BMAL1circadian expression and clock rhythmicity. This reveals anadditional level of regulation within the core mechanism ofthe 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, Universityof Kuopio, 70211 Kuopio, Finland.
To whom correspondence should be addressed. E-mail: paolosc{at}igbmc.u-strasbg.fr
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