In 2018, together with
Prof. David Virshup from DukeNUS, we discovered that the two alternatively spliced isoforms of Casein Kinase 1 Delta (Ck1d1 and Ck1d2), reported in databases but of functions unknown, had different kinase activities. CK1D is known to regulate the circadian clock by phosphorylating the PER2 protein, leading to the degradation or stabilization of PER2, depending on which residue is phosphorylated, leading to the acceleration or deceleration of the pace of the clock, respectively. Surprisingly, while an increase in CK1D1 activity accelerates the clock, increasing the activity of CK1D2 slows the clock down. Moreover, these isoforms are expressed in a tissue-specific manner, and their alternative transcripts are strongly regulated, notably by
N6-adenosine methylation (
Fustin et al., 2018;
Narasimamurthy et al., 2018). We are currently investigating how their expression is regulated, and what their respective physiological functions and association with pathologies are.
The methyl or methionine cycle is a key metabolic pathway linking methionine with the synthesis of
S-adenosylmethionine, the methyl donor co-substrate used by many methyltransferases (over 600 identified so far in the human genome) for the methylation of nucleic acids, proteins, fatty acids and many other biomolecules.
