期刊
SCIENCE
卷 302, 期 5644, 页码 439-442出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1086593
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资金
- NHLBI NIH HHS [HL67007, R01 HL067007] Funding Source: Medline
- NIGMS NIH HHS [GM07143] Funding Source: Medline
- NINDS NIH HHS [NS35859, NS22155, NS11158, NS10170, R01 NS022155, R01 NS035859, NS11134] Funding Source: Medline
Despite a central circadian role in Drosophila for the transcriptional regulator Timeless (dTim), the relevance of mammalian Timeless (mTim) remains equivocal. Conditional knockdown of mTim protein expression in the rat suprachiasmatic nucleus (SCN) disrupted SCN neuronal activity rhythms, and altered levels of known core clock elements. Full-length mTim protein (mTIM-fl) exhibited a 24-hour oscillation, whereas a truncated isoform (mTIM-s) was constitutively expressed. mTIM-fl associated with the mammalian clock Period proteins (mPERs) in oscillating SCN cells. These data suggest that mTim is required for rhythmicity and is a functional homolog of dTim on the negative-feedback arm of the mammalian molecular clockwork.
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