Kid-1 participates in regulating ERK phosphorylation as a part of the circadian clock output in rat kidney.

Circadian clock genes play a role for the regulation of cell cycle, but the factors connecting clock to cell cycle are not fully understood. We found that mRNA of Kid-1--a zinc-finger-type transcriptional repressor was localized to cortical and juxtamedullary segments of tubules but not to glomeruli in the rat kidney. Kid-1 mRNA showed robust circadian oscillation with a peak at ZT16. Under temporal restricted feeding, the phase of the oscillation shifted along with mRNAs of the clock genes--Per1 and Per2. The rhythm of S-phase in cell cycle disappeared in the kidney under the restricted feeding. The level of phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 was rhythmic with a peak at ZT16 in the kidney. We found that knockdown and overexpression of Kid-1 in NRK52E (normal rat kidney epithelial) cells induced and reduced the phosphorylation of ERK1/2, respectively. The data suggest that clock-controlled Kid-1 regulates the cell cycle of proliferating renal tubular epithelial cells through ERK phosphorylation.

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