The DOUBLETIME protein kinase regulates phosphorylation of the <i>Drosophila</i> PDP1&egr;

다국어 초록 (Multilingual Abstract)

<P>Abstract</P><P>Reversible phosphorylation of clock proteins plays an important role in circadian timekeeping as it is a key post-translational mechanism that regulates the activity, stability and subcellular localization of core clock proteins. The kinase DOUBLETIME (DBT), a <I>Drosophila</I> ortholog of mammalian casein kinase I&egr;, regulates circadian phosphorylation of two essential clock proteins, PERIOD and dCLOCK. We present evidence that <I>Par Domain Protein 1&egr;</I> (PDP1&egr;), a transcription factor and mediator of clock output in <I>Drosophila</I>, is phosphorylated <I>in vivo</I> and in cultured cells by DBT activity. We also demonstrate that DBT interacts with PDP1&egr; and promotes its degradation by the ubiquitin-proteasome pathway in cultured cells. In addition, PDP1&egr; nuclear localization is decreased by <I>dbt</I> RNA interference in S2 cell system. These results suggest that DBT regulates phosphorylation, stability and localization of PDP1&egr;, and that it has multiple targets in the <I>Drosophila</I> circadian system.</P>