Mammalian circadian autoregulatory loop:: A timeless ortholog and mPer1 interact and negatively regulate CLOCK-BMAL1-induced transcription

被引：306
作者：
Sangoram, AM
Saez, L
Antoch, MP
Gekakis, N
Staknis, D
Whiteley, A
Fruechte, EM
Vitaterna, MH
Shimomura, K
King, DP
Young, MW
Weitz, CJ
Takahashi, JS
机构：
[1] Northwestern Univ, Dept Neurobiol & Physiol, Evanston, IL 60208 USA
[2] Northwestern Univ, Natl Sci Fdn Ctr Biol Timing, Evanston, IL 60208 USA
[3] Northwestern Univ, Howard Hughes Med Inst, Evanston, IL 60208 USA
[4] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA
[5] Rockefeller Univ, Genet Lab, New York, NY 10021 USA
[6] Rockefeller Univ, Natl Sci Fdn Ctr Biol Timing, New York, NY 10021 USA
来源：
NEURON | 1998年 / 21卷 / 05期
关键词：
D O I：
10.1016/S0896-6273(00)80627-3
中图分类号：
Q189 [神经科学];
学科分类号：
071006 ;
摘要：
We report the cloning and mapping of mouse (mTim) and human (hTIM) orthologs of the Drosophila timeless (dtim) gene. The mammalian Tim genes are widely expressed in a variety of tissues; however, unlike Drosophila, mTim mRNA levels do not oscillate in the suprachiasmatic nucleus (SCN) or retina. Importantly, hTIM interacts with the Drosophila PERIOD (dPER) protein as well as the mouse PER1 and PER2 proteins in vitro. In Drosophila (S2) cells, hTIM and dPER interact and translocate into the nucleus. Finally, hTIM and mPER1 specifically inhibit CLOCK-BMAL1-induced transactivation of the mPer1 promoter. Taken together, these results demonstrate that mTim and hTIM are mammalian orthologs of timeless and provide a framework for a basic circadian autoregulatory loop in mammals.
引用
收藏
页码：1101 / 1113
页数：13
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