Circadian clock control by SUMOylation of BMAL1.
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.
Cardone
Luca
L
Institut de Génétique et de Biologie Moléculaire et Cellulaire, 1 rue Laurent Fries, 67404 Illkirch, Strasbourg, France.
Hirayama
Jun
J
Giordano
Francesca
F
Tamaru
Teruya
T
Palvimo
Jorma J
JJ
Sassone-Corsi
Paolo
P
D056930:ARNTL Transcription Factors; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D056926:CLOCK Proteins; D019556:COS Cells; D018797:Cell Cycle Proteins; D002460:Cell Line; D002940:Circadian Rhythm; D019281:Dimerization; D005033:Ethylmaleimide / Q000494:pharmacology; D005786:Gene Expression Regulation; D008099:Liver / Q000378:metabolism; D008239:Lysine / Q000378:metabolism; D051379:Mice; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D056950:Period Circadian Proteins; D010766:Phosphorylation; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D025842:SUMO-1 Protein / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D056930:ARNTL Transcription Factors; D051792:Basic Helix-Loop-Helix Proteins; D056926:CLOCK Proteins; D018797:Cell Cycle Proteins; D005033:Ethylmaleimide; D008239:Lysine; D009687:Nuclear Proteins; D056950:Period Circadian Proteins; D011993:Recombinant Fusion Proteins; D025842:SUMO-1 Protein; D015534:Trans-Activators; D014157:Transcription Factors; C538961:Bmal1 protein, mouse; C539023:Per1 protein, mouse; C538944:Clock protein, mouse