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

Autor: Sangoram AM; Department of Neurobiology and Physiology and National Science Foundation, Center for Biological Timing, The Rockefeller University, New York, New York 10021, USA., Saez L, Antoch MP, Gekakis N, Staknis D, Whiteley A, Fruechte EM, Vitaterna MH, Shimomura K, King DP, Young MW, Weitz CJ, Takahashi JS
Jazyk: angličtina
Zdroj: Neuron [Neuron] 1998 Nov; Vol. 21 (5), pp. 1101-13.
DOI: 10.1016/s0896-6273(00)80627-3
Abstrakt: 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.
Databáze: MEDLINE