Circadian Clock Control by SUMOylation of BMAL1
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.
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References and Notes
1
G. Gill, Curr. Opin. Genet. Dev.13, 108 (2003).
2
S. Muller, C. Hoege, G. Pyrowolakis, S. Jentsch, Nat. Rev. Mol. Cell Biol.2, 202 (2001).
3
G. Gill, Genes Dev.18, 2046 (2004).
4
J. M. Desterro, M. S. Rodriguez, R. T. Hay, Mol. Cell2, 233 (1998).
5
M. J. Matunis, J. Wu, G. Blobel, J. Cell Biol.140, 499 (1998).
6
S. Salinas et al., J. Cell Biol.165, 767 (2004).
7
S. J. Li, M. Hochstrasser, Nature398, 246 (1999).
8
D. Bailey, P. O'Hare, J. Biol. Chem.279, 692 (2003).
9
J. C. Dunlap, Cell96, 271 (1999).
10
M. W. Young, S. A. Kay, Nat. Rev. Genet.2, 702 (2001).
11
P. L. Lowrey, J. S. Takahashi, Annu. Rev. Genet.34, 533 (2000).
12
Z. J. Huang, I. Edery, M. Rosbash, Nature364, 259 (1993).
13
R. N. Freiman, R. Tjian, Cell112, 11 (2003).
14
Single-letter abbreviations for the amino acid residues are as follows: A, Ala; C, Cys; D, Asp; E, Glu; F, Phe; G, Gly; H, His; I, Ile; K, Lys; L, Leu; M, Met; N, Asn; P, Pro; Q, Gln; R, Arg; S, Ser; T, Thr; V, Val; W, Trp; and Y, Tyr.
15
T. Kamitani, H. P. Nguyen, E. T. Yeh, J. Biol. Chem.272, 14001 (1997).
16
L. Cardoneet al., data not shown.
17
T. Sternsdorf, K. Jensen, B. Reich, H. Will, J. Biol. Chem.274, 12555 (1999).
18
U. Schibler, P. Sassone-Corsi, Cell111, 919 (2002).
19
T. Suzuki et al., J. Biol. Chem.274, 31131 (1999).
20
C. Lee, J. P. Etchegaray, F. R. Cagampang, A. S. Loudon, S. M. Reppert, Cell107, 855 (2001).
21
T. Tamaru et al., Genes Cells8, 973 (2003).
22
N. Cermakian, P. Sassone-Corsi, Nat. Rev. Mol. Cell Biol.1, 59 (2000).
23
R. V. Kondratov et al., Genes Dev.17, 1921 (2003).
24
H. Okamura, J. Biol. Rhythms19, 388 (2004).
25
T. K. Darlington et al., Science280, 1599 (1998).
26
E. A. Griffin, D. Staknis, C. J. Weitz, Science286, 768 (1999).
27
N. Cermakian, L. Monaco, M. P. Pando, A. Dierich, P. Sassone-Corsi, EMBO J.20, 3967 (2001).
28
G. T. van der Horst et al., Nature398, 627 (1999).
29
M. P. Antoch et al., Cell89, 655 (1997).
30
A. Balsalobre, F. Damiola, U. Schibler, Cell93, 929 (1998).
31
M. K. Bunger et al., Cell103, 1009 (2000).
32
Materials and methods are available as supporting material on Science Online.
33
We thank C. Bradfield, J. Walisser, U. Schibler, J. Takahashi, N. Kotaja, D. Bailey, F. Melchior, A. Dejean, R. Hay, M. Doi, I. K. Ullas, I. Yujnovsky, and S. Cho for discussions and sharing of reagents and E. Heitz and C. Berling for technical assistance. L.C. is supported by a long-term European Molecular Biology Organization fellowship, J.H. is supported by a fellowship of the Fondation de la Recherche Médicale. Work in our laboratory is supported by Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Centre Hospitalier Universitaire Régional, Fondation de la Recherche Médicale, Université Louis Pasteur, Electricité de France, Association pour la Recherche sur le Cancer, and La Ligue Contre le Cancer.
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Science
Volume 309 | Issue 5739
26 August 2005
26 August 2005
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American Association for the Advancement of Science.
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Received: 4 February 2005
Accepted: 25 July 2005
Published in print: 26 August 2005
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